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Category : Nanomedicine

Healthcare Nanotechnology (Nanomedicine) Market Research Report with Revenue, Gross Margin, Market Share and Future Prospects till 2026 – The Market…

The Healthcare Nanotechnology (Nanomedicine) Market grew in 2019, as compared to 2018, according to our report, Healthcare Nanotechnology (Nanomedicine) Market is likely to have subdued growth in 2020 due to weak demand on account of reduced industry spending post Covid-19 outbreak. Further, Healthcare Nanotechnology (Nanomedicine) Market will begin picking up momentum gradually from 2021 onwards and grow at a healthy CAGR between 2021-2025

Deep analysis about market status (2016-2019), competition pattern, advantages and disadvantages of products, industry development trends (2019-2025), regional industrial layout characteristics and macroeconomic policies, industrial policy has also been included. From raw materials to downstream buyers of this industry have been analysed scientifically. This report will help you to establish comprehensive overview of the Healthcare Nanotechnology (Nanomedicine) Market

Get a Sample Copy of the Report at: https://i2iresearch.com/report/global-healthcare-nanotechnology-(nanomedicine)-market-2020-market-size-share-growth-trends-forecast-2025/#download-sample

The Healthcare Nanotechnology (Nanomedicine) Market is analysed based on product types, major applications and key players

Key product type:NanomedicineNano Medical DevicesNano DiagnosisOther

Key applications:AnticancerCNS ProductAnti-infectiveOther

Key players or companies covered are:AmgenTeva PharmaceuticalsAbbottUCBRocheCelgeneSanofiMerck & CoBiogenStrykerGilead SciencesPfizer3M CompanyJohnson & JohnsonSmith & NephewLeadiant BiosciencesKyowa Hakko KirinShireIpsenEndo International

The report provides analysis & data at a regional level (North America, Europe, Asia Pacific, Middle East & Africa , Rest of the world) & Country level (13 key countries The U.S, Canada, Germany, France, UK, Italy, China, Japan, India, Middle East, Africa, South America)

Inquire or share your questions, if any: https://i2iresearch.com/report/global-healthcare-nanotechnology-(nanomedicine)-market-2020-market-size-share-growth-trends-forecast-2025/

Key questions answered in the report:1. What is the current size of the Healthcare Nanotechnology (Nanomedicine) Market, at a global, regional & country level?2. How is the market segmented, who are the key end user segments?3. What are the key drivers, challenges & trends that is likely to impact businesses in the Healthcare Nanotechnology (Nanomedicine) Market?4. What is the likely market forecast & how will be Healthcare Nanotechnology (Nanomedicine) Market impacted?5. What is the competitive landscape, who are the key players?6. What are some of the recent M&A, PE / VC deals that have happened in the Healthcare Nanotechnology (Nanomedicine) Market?

The report also analysis the impact of COVID 19 based on a scenario-based modelling. This provides a clear view of how has COVID impacted the growth cycle & when is the likely recovery of the industry is expected to pre-covid levels.

Contact us:i2iResearch info to intelligenceLocational Office: *India, *United States, *GermanyEmail: [emailprotected]Toll-free: +1-800-419-8865 | Phone: +91 98801 53667

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Healthcare Nanotechnology (Nanomedicine) Market Research Report with Revenue, Gross Margin, Market Share and Future Prospects till 2026 - The Market...

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Research: A new website for the essence of COINS – Tdnews

Photo:COINS aims to realize in-body hospitals , which integrates all medical functions within the body.Smart nanomachines of a virus size will autonomously patrol the microenvironments in the body and provide diagnosticview more

Credit Image: 2020 Innovation Center of NanoMedicine

Summary

Main body

As the Kawasaki hub (COINS) of the Center of Innovation (COI) Program of the Ministry of Education, Culture, Sports, Science and Technology, the KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION Innovation Center of NanoMedicine (Director General: Kazunori Kataoka, Location; Tonomachi Kawasaki City, Abbreviation: iCONM) aiming to establish in-body hospitals by 2045 has opened a new website for Project COINS.

The contents were exhibited at Innovation JAPAN2020, that was an online matching event between Academia and Industry, organized by JST (Japan Science and Technology Agency).https://ij2020online.jst.go.jp/

COINS will continue to work for creating the innovation towards the most innovative hub in the world. We have posted what COINS thinks of 2045 and the roadmap in easy-to-understand manner. Please visit our website.https://coins.kawasaki-net.ne.jp/en/about/

Information on new website URL

In English??https://coins.kawasaki-net.ne.jp/en/about/

In Japanese ?https://coins.kawasaki-net.ne.jp/about/

The official website remains https://coins.kawasaki-net.ne.jp/en/

###

Public Interest Incorporated Foundation KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION

KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION was established in 1988 funded 100% from Kawasaki City for the purpose of coping with the hollowing out of industry and changes in the demand structure. In order to realize a higher level of market development, transforming R&D type companies, training technological capabilities to support it, human resources development, understanding market needs, etc., by utilizing the functions of the Kawasaki, KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION has been contributing to revitalize the local economy by promoting exchanges of local industry information, advancing technology and corporate exchanges with establishment of a R&D institutions, developing creative human resources through workshops and promoting businesses such as expanding sales channels through exhibition business.http://www.kawasaki-net.ne.jp/

Innovation Center of NanoMedicine (iCONM)

Innovation Center of NanoMedicine (iCONM) started its operation in April 2015 as a core research center in life science field at King SkyFront on the request of Kawasaki city that KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION utilized national policies as a business operator and proposer.It is a unique research center that the world has ever seen which is designed for the purpose of promoting open innovation through industry-academia-government/medical-engineering collaboration, prepared with state-of-the-art facilities and experimental equipment, that enables comprehensive research and development from organic synthesis / microfabrication to preclinical testing. https://iconm.kawasaki-net.ne.jp/en/

Center of Innovation Program (COI)

The COI program is a research and development program under the Ministry of Education, Culture, Sports, Science and Technology and the Japan Science and Technology Agency. The program employs the backcasting approach and set interdisciplinary and collaborative R&D themes that should be challenged at the present from the issues that are underlying in the future society. Eighteen centers have been established nationwide to realize radical innovation through industry-academia collaboration which cannot be accomplished by industry and academia alone.The Kawasaki center is the only COI center managed by local governments, not universities, and the research projects carried out there are called COINS (Center of Open Innovation Network for Smart Health).

COI: https://www.jst.go.jp/tt/EN/platform/coi.html

COINS: https://coins.kawasaki-net.ne.jp/en/

November 25, 2020

Inquiries

KAWASAKI INSTITUTE OF INDUSTRIAL PROMOTION

Innovation Center of NanoMedicine (iCONM)

COINS Research Promotion Office / Person in charge: Mami Satake

Email: [emailprotected]

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Research: A new website for the essence of COINS - Tdnews

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Global Nanomedicine Market Top Countries Analysis and Manufacturers With Impact of COVID-19 | 2020-2026 Detail Analysis focusing on Application, Types…

Databridgemarketresearch.com Present Global Nanomedicine Market Industry Trends and Forecast to 2027 new report to its research database. The report spread No of pages: 350 No of Figures: 60 No of Tables: 220 in it. This Global Nanomedicine Market report takes into consideration diverse segments of the market analysis that todays business ask for. The Global Nanomedicine Market report provides estimations of CAGR values, market drivers and market restraints about the industry which are helpful for the businesses in deciding upon numerous strategies. The base year for calculation in the report is taken as 2017 whereas the historic year is 2016 which will tell you how the Global Nanomedicine Market is going to perform in the forecast years by informing you what the market definition, classifications, applications, and engagements are. The report helps you to be there on the right track by making you focus on the data and realities of the industry.

The research studies of this Global Nanomedicine Market report helps to evaluate several important parameters that can be mentioned as investment in a rising market, success of a new product, and expansion of market share. Market estimations along with the statistical nuances included in this market report give an insightful view of the market. The market analysis serves present as well as future aspects of the market primarily depending upon factors on which the companies contribute in the market growth, crucial trends and segmentation analysis. This Global Nanomedicine Market research report also gives widespread study about different market segments and regions.

Global nanomedicine marketis registering a healthy CAGR of 15.50% in the forecast period of 2019-2026. This rise in the market value can be attributed to increasing number of applications and wide acceptance of the product globally. There is a significant rise in the number of researches done in this field which accelerate growth of nanomedicine market globally.

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Key Market Competitors

Few of the major market competitors currently working in the global nanomedicine market are Abbott, Invitae Corporation, General Electric Company, Leadiant Biosciences, Inc., Johnson & Johnson Services, Inc., Mallinckrodt, Merck Sharp & Dohme Corp., NanoSphere Health Sciences, Inc., Pfizer Inc., CELGENE CORPORATION, Teva Pharmaceutical Industries Ltd., Gilead Sciences, Inc., Amgen Inc., Bristol-Myers Squibb Company, AbbVie Inc., Novartis AG, F. Hoffmann-La Roche Ltd., Luminex Corporation, Eli Lilly and Company, Nanobiotix, Sanofi, UCB S.A., Ablynx among others.

Competitive Landscape

Global nanomedicine market is highly fragmented and the major players have used various strategies such as new product launches, expansions, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of nanomedicine market for global, Europe, North America, Asia-Pacific, South America and Middle East & Africa.

Key Insights in the report:

Complete and distinct analysis of the market drivers and restraints

Key Market players involved in this industry

Detailed analysis of the Market Segmentation

Competitive analysis of the key players involved

Market Drivers are Restraints

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Market Segmentation:-

By Product Type

By Application

By Indication

By Modality

To comprehend Global Nanomedicine market dynamics in the world mainly, the worldwide Nanomedicine market is analyzed across major global regions.

Actual Numbers & In-Depth Analysis, Business opportunities, Market Size Estimation Available in Full Report.

Some of the Major Highlights of TOC covers:

Chapter 1: Methodology & Scope

Definition and forecast parameters

Methodology and forecast parameters

Data Sources

Chapter 2: Executive Summary

Business trends

Regional trends

Product trends

End-use trends

Chapter 3: Industry Insights

Industry segmentation

Industry landscape

Vendor matrix

Technological and innovation landscape

For More Insights Get Detailed TOC @https://www.databridgemarketresearch.com/toc/?dbmr=global-nanomedicine-market

Nanomedicine Market report effectively provides required features of the global market for the population and for the business looking people for mergers & acquisitions, making investments, new vendors or concerned in searching for the appreciated global market research facilities. It offers sample on the size, offer, and development rate of the market. The Nanomedicine report provides the complete structure and fundamental overview of the industry market.

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Global Nanomedicine Market Top Countries Analysis and Manufacturers With Impact of COVID-19 | 2020-2026 Detail Analysis focusing on Application, Types...

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Protein-avoidant ionic liquid (PAIL)coated nanoparticles to increase bloodstream circulation and drive biodistribution – Science Advances

Abstract

The rapid clearance of intravenously administered nanoparticles (NPs) from the bloodstream is a major unsolved problem in nanomedicine. Here, we describe the first use of biocompatible protein-avoidant ionic liquids (PAILs) as NP surface modifiers to reduce opsonization. An ionic liquid choline hexenoate, selected for its aversion to serum proteins, was used to stably coat the surface of poly(lactic-co-glycolic acid) (PLGA) NPs. Compared with bare PLGA and poly(ethylene glycol)coated PLGA particles, the PAIL-PLGA NPs showed resistance to protein adsorption in vitro and greater retention in blood of mice at 24 hours. Choline hexenoate redirected biodistribution of NPs, with preferential accumulation in the lungs with 50% of the administered dose accumulating in the lungs and <5% in the liver. Lung accumulation was attributed to spontaneous attachment of the PAIL-coated NPs on red blood cells in vivo. Overall, ionic liquids are a promising class of materials for NP modification for biomedical applications.

Nanomedicine offers an alluring promise for drug deliverythe capacity to administer therapeutics to specific parts of the body while minimizing off-target effects seen with systemic administration of drugs, particularly chemotherapeutics (1). However, despite decades of excellent work in the field, only a handful of nanoparticles (NPs) have made it through clinical trials (2). One large barrier to translation of nanomedicines is the removal of the NPs from the bloodstream (3). Once injected intravenously, the NPs encounter a diversity of serum proteins that adhere to the surface of the particle to form a protein corona (4), alerting the immune system to a foreign invader, which then swiftly removes the vast majority of the injected NPs to the filtering organs, primarily the liver (5), for clearance from the body.

The current gold standard for reducing NP clearance is the use of poly(ethylene) glycol (PEG) coatings, which reduces clearance by increasing the hydrophilicity of the surface of the particle, thwarting the attachment of the circulating proteins (6). However, the widespread usage of PEG in many consumer products, and the simplicity of its chemical structure, has led to an estimated 25% of the general population developing anti-PEG antibodies (7), mainly anti-PEG immunoglobulin M (8). A recent clinical review of the immunogenicity of PEG included a report of the use of PEGylated uricase for the treatment of critical gout. Of 169 human patients, 89% developed high anti-pegloticase antibody response (9), which resulted in rapid clearance and injection-site reactions after the first injection, overwhelming any beneficial effect of the administered therapeutic. Therefore, strategies to avoid NP clearance that require alternatives to PEG are needed in the toolbox of nanomedicine.

Ionic liquids (ILs), which consist of asymmetric, bulky cations and anions that have melting points below 100C (10), have been used across a broad range of applications, including synthesis (11), catalysis (12), and battery applications (13). They have a number of appealing properties, one of which is inherent tunability, where a small change in the chemical structure of one of the components results in a measurable shift in observed bulk properties (14). When synthesized from biocompatible materials, ILs have shown great promise in biomedical applications (15), including stabilizing proteins (16), drug delivery through the skin (1719), and oral drug delivery (20), where the components of ILs can be selected to optimize physiologically relevant properties, such as membrane interaction (21). ILs have been used to coat NPs in nonbiological settings, such as catalysis (22) and sensing platforms (23), and some preliminary studies have evidenced their suitability in improving the biocompatibility of existing carriers (24). However, the versatility and tunability of ILs have not yet been exploited in the context of coating NPs to reduce opsonization in intravenous drug delivery. We hypothesized that ILs can be designed to coat NPs to reduce protein adsorption and opsonization. This hypothesis was inspired by the success of zwitterionic surfactants in reducing surface protein adsorption (25, 26). Here, we developed and synthesized a library of biocompatible ILs and screened for those that do not solvate proteins wellso-called protein-avoidant ionic liquids (PAILs). Upon incubation with NPs, PAILs spontaneously coat the surface of NPs with PAILs and form a stable coating. PAIL coating delays protein adsorption on the NP surface and reduces clearance of intravenously injected NPs in vivo.

Poly(lactic-co-glycolic acid) (PLGA) was chemically conjugated to 1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt solid (DiD) dye, and PLGA NPs were synthesized by surfactant-free nanoprecipitation to generate bare control NPs (see Methods). PEG was chemically conjugated to PLGA NPs to generate PEGylated-PLGA NPs. A library of choline-based ILs was synthesized to coat NPs (table S1). Choline was used as a cation because of its biocompatibility and prior history of use in humans. Choline is a dietary supplement and closely related to a neurotransmitter acetyl choline (27). Various anions were used to synthesize ILs. A range of carboxylic acidbased anions were tested, with carbon chain lengths of four to eight and with varying unsaturation, ring structures, and number of oxygen atoms. Ion ratios of 1:1 to 1:6 (cation:anion) were also tested. ILs were allowed to coat NPs through a 3-hour incubation with stirring, followed by filtration. The synthesized NPs were then characterized with nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM; for the choline hexenoate 1:2 particles). The ability of ILs to coat NPs was confirmed by NMR (presence of IL components), DLS (changes in NP sizes), and TEM for the lead IL, choline hexenoate.

The capping ability of ILs varied greatly with their composition. ILs were considered to have successfully capped the PLGA NP if, after the modification and filtration process, monodispersed [polydispersity index (PDI), <0.3] peaks appeared by DLS with hydrodynamic diameters <300 nm. ILs with ring structures, presence of oxygen atoms beyond the carboxylic acid functional group, and unbranched carbon chains shorter than six were not able to stably cap the NPs. Ion ratio also affected NP capping. Among the ILs with eight carbon anions, 1:2 octanoic acid created much smaller particles than its 1:1 counterpart. In the case of geranic acid, all ion ratios produced stably capped particles except 1:6. Figure 1 shows the full characterization of particles coated with choline hexenoate 1:2.

(A) 1H NMR spectrum of PLGA NPs surface coated with choline hexenoate (1:2). (B) DLS reported hydrodynamic diameter of NPs (log10 transformation on the x axis) when bare (black), coated with PEG (blue), and coated with IL (red) with mean diameters above each curve. (C) DLS reported zeta potential of NPs when bare (black), coated with PEG (blue), and coated with IL (red). (D) TEM of bare PLGA particles. (E) TEM of PEG-capped particles. (F) TEM of IL-coated particles. Scale bars, 200 nm.

Presence of choline hexenoate on NPs was confirmed by proton NMR (Fig. 1A). From integration of the peaks corresponding to the choline and hexenoate, each component appears in molar equivalencyi.e., 1:1, despite adding a 1:2 ratio to the synthesis procedure. Addition of choline hexenoate slightly increased the diameter of the NPs as measured by DLS (Fig. 1B). Bare PLGA NPs (black) had an average diameter of 64.60 9.41 nm (PDI = 0.135). PEGylation increased the NP diameter to 123.1 14.8 nm (PDI = 0.2) (blue). IL-NPs (red) exhibited the largest diameter of 170.0 19.1 nm (PDI = 0.16) (Fig. 1C). Corresponding changes were also observed in the surface charge of the NPs. Bare NPs (black) had the average zeta potential of 11.0 4.03 mV. PEGylated NPs (blue) had a zeta potential of 31.3 5.86 mV. IL-NPs (red) exhibited the most negative surface charge of 40.5 2.12 mV. TEM indicated substantial changes in the morphologies of NPs (Fig. 1D). Bare PLGA NPs exhibited uniform composition, and size of NPs generally matched those determined from DLS. PEGylated NPs exhibited a high-contrast core surrounded by a ring of lower contrast around the PLGA core (Fig. 1E). IL-NPs exhibited a peculiar structure where the high-contrast core was surrounded by a much larger core of lighter contrast than the polymeric core (Fig. 1E), evidencing the successful surface modification of the PLGA NPs. Figure S4 shows the population size distribution (BD) by TEM. The IL-NPs retained this size and negative surface charge with an acceptable PDI for >3 weeks (figs. S1 to S3), only falling apart at 3.5 weeks, at which point the ester linkages in the PLGA likely begin to undergo hydrolysis (28), as seen by the PDI of the bare particles approaching 1 at the 3.5-week mark. This is consistent with earlier reports of 50:50 PLGA particles undergoing in vitro degradation after 21 to 26 days (29).

The serum stability and compatibility of IL-NPs were tested by incubating them with whole-mouse serum. IL-NPs maintained their stability in serum for various periods of time depending on the IL composition (table S2). IL-NPs resisted size increase for a composition-dependent time period, followed by a monotonic size increase. The duration of no size growth was considered as an indicator of the ability of IL-NPs to resist protein corona formation.

The identity of the anion played a significant role in protecting the NP from protein adsorption. Anions with carbon chains six to eight carbons in length emerged as the best at resisting protein adsorption. The role of the double bond emerged as a critical factorthe addition of a double bond to hexanoate to create hexenoate improved the resistance to serum by a factor of 22. In the case of the serum test, the role of the ion ratio is anion dependent. For the hexenoate, the 1:2 ratio outperforms the 1:1 IL by sixfold, but for geranic acid, the 1:1 ratio outperforms the others by twofold.

The most successful candidate of the library of ILs tested was choline hexenoate (1:2). Therefore, it underwent further testing and is hereafter referred to as PAIL.

Stability of NPs against aggregation was tested in undiluted mouse serum in a timed DLS test. The diameter of bare PLGA particles, shown as black diamonds, increased within minutes to 200% of their original size (Fig. 2A). This is consistent with numerous reports on the formation of protein coronae on polymeric particles (6, 7, 30). The PEGylated particles (blue circles) fared better than the bare NPs, only growing 60% larger than their original measured size in buffer over 30 min. The PAIL-coated particles (red squares) exhibited no appreciable size change even after 60 min in neat serum, only changing size after 90 min. The surface charge of the particles was measured at the conclusion of the serum test (Fig. 2B). The surface of the bare particles is very close to neutral, while both the PEG and PAIL show zeta potentials of 15 mV. SDSpolyacrylamide gel electrophoresis (SDS-PAGE) was performed to qualitatively investigate the degree of protein adsorption after 2 and 20 min in neat serum, evidencing that the PAIL-coated particles show a significantly smaller degree of protein adsorption. In vitro hemolysis of the particles was assessed with isolated mouse red blood cells (RBCs) (Fig. 2C). All particles showed minimal (<10%) hemolysis [no significant difference by analysis of variance (ANOVA) analysis, P = 0.96], indicating their suitability for further intravenous testing.

(A) Relative percentage increase in NP hydrodynamic diameter over time in serum from original size by DLS (n = 4), with bare NPs shown in black, PEGylated NPs in blue, and PAIL-NPs in red. (B) Zeta potential (n = 3) measured at the final time point, showing that PEG and PAIL-capped particles have a similar surface charge. (C) SDS-PAGE from a 12% gel with tris-Gly running buffer. Left to right: Ladder, PLGA 2 min, PLGA 20 min, PEG 2 min, PEG, 20 min, IL 2 min, IL 20 min. (D) Hemolysis (n = 4) of mouse RBCs in vitro show ILs do not induce significantly more hemolysis than controls (one-way ANOVA, P = 0.9586, F = 0.0425). All experiments were performed ex vivo with at least duplicate internal readings/sample/trial. All error bars are reported in SEM.

PAIL-NPs were administered intravenously via tail vein into healthy BALB/c mice (Fig. 3A). Bare NPs exhibited rapid clearance with only 20% NPs remaining in circulation after 20 min (black diamonds). PEGylated NPs exhibited improved circulation over bare NPs with 14.2 2.7% NPs remaining in circulation after 24 hours. PAIL-NPs exhibited the highest circulation with 23.6 0.86% NPs remaining in circulation after 24 hours (P = 0.02 between PEG and PAIL-NPs). At the conclusion of the 24 hours, the major organs were excised, examined by IVIS (in vivo imaging system) imaging (Fig. 3C), and quantified by fluorescence spectroscopy (Fig. 3B).

(A) Mouse 24-hour in vivo bloodstream circulation profile. Percentage of tail veininjected dose measured at each time point, with bare particles in black, PEG coated in blue, and IL coated in red. n = 6. IL-coated particles outperform PEG particles and are significantly more highly detected than uncoated PLGA NPs at 24 hours (one-way ANOVA; 24 hours: P = 0.000031, F = 22.47, followed by t test: paired two-tailed sample for means: P = 0.00202). (B) In vivo organ biodistribution profile of NPs at 24 hours by major blood-filtering organs. Represented as percentage of tail veininjected dose. Inset shows the direct [lung:liver] ratio of the IL, PEG, and bare NPs. n = 6, ***P < 0.001,**P < 0.01, and *P < 0.05 (one-way ANOVA verified by t test: paired two-tailed sample for means). (C) Twenty-four hours post IV injection activated in vivo mouse IL-6 concentrations in the plasma (pg/ml). (n = 4), t test: paired two-tailed sample for means: **P < 0.005, ***P < 0.001, and ****P < 0.0001. (D) Representative IVIS images of whole major blood-filtering organs at 24 hours after injection. All error bars are reported as standard error of the mean.

In the case of the bare particles (Fig. 3B, black), 50% of the administered dose accumulated in the liver. Most of the PEGylated particles (blue) were also found in the liver 24 hours after injection. The PAIL-NPs, however, were predominately located in the lungs, with 50% of the administered dose accumulating in the lungs. High lung/liver ratio was observed for PAIL-NPs (~12), which was >200-fold greater than that for bare NPs or PEGylated NPs. IVIS images confirmed high lung accumulation of PAIL-NPs (Fig. 3D). The IVIS images of the major organs of all six mice across the treatment groups can be found in figs. S5 to S7. Note that the fluorescence that appears in the brain across all treatment groups is likely to be autofluorescence and does not reflect any accumulation of NPs in the brain.

Systemic toxicity of IL-NPs was assessed by measuring interleukin-6 (IL-6) in the blood to investigate the possibility of inflammation induced by NPs 24 hours after injection. Both the bare and PEGylated particles show significant levels of IL-6 at a concentration of ca. 100 pg/ml, while the PAIL-NPs show >2-fold lower values at <40 pg/ml (Fig. 3C).

To investigate the reason for high lung accumulation of PAIL-NPs, RBCs from mice were evaluated by both SEM and fluorescence-activated cell sorting (FACS). Figure 4 (A and B) shows the RBCs after injecting bare (A) and PEG-PLGA particles (B). RBCs harvested from mice injected with PAIL-NPs indicated presence of NPs on the RBC surface (Fig. 4C). These NPs were not seen in mice injected with bare NPs (Fig. 4A). RBCs were also incubated with PAIL-NPs in vitro and exhibited attachment (Fig. 4D). The imaged RBCs and plasma were also analyzed using FACS. Figure 4 (E and F) shows the results for RBC and plasma after injection of bare PLGA particles, where no fluorescence is observed when gated for the DiD dye in the RBC fraction, but a large amount of fluorescence appears in the plasma. PAIL-NPs, however, exhibited high attachment to RBCs (Fig. 4G) and minimal presence in the plasma (Fig. 4H).

(A to D) SEM of RBCs withdrawn from mice after being treated with (A) bare PLGA NPs, (B) PEG-PLGA NPs, and (C) PAIL-NPs. (D) PAIL-NPs treated in vitro. Scale bars, 400 nm. Black arrows indicate NPs. (E and F) FACS 24 hours after injection of (E) bare NPs RBCs, (F) bare NPs in plasma, (G) PAIL-NPs in RBCs, and (H) PAIL-NPs in plasma.

The clearance of NPs from the bloodstream after intravenous injection remains a pressing issue even as new, promising, nanomedicines are reported near daily. Agents other than PEG are needed to overcome the immune challenges generated by its overuse. PLGA NPs were successfully coated with choline hexenoate to generate PAIL-NPs (Fig. 1). The PAIL-NPs exhibit a larger hydrodynamic radius and a more negative surface charge compared with the bare and PEGylated particles, indicating successful modification. The PLGA core has a slight negative surface charge, meaning that the layer closest to the core consists of the cation. The final, negative surface charge of the particle indicates that the terminal layer consists of anions.

The arrangement of ILs at a charged surface is a well-known phenomenon in contexts such as electrochemistry, where the ionic components arrange spontaneously in an alternating fashion at a charged surface, such as an electrode, to form an electrical double layer. Atkin and Warr (31) used atomic force microscopy to analyze ILs at mica, silica, and graphite surfaces, finding that the cations and anions arranged in alternating layers and that each layer was approximately 1 nm thick. This modification process can be likened to a layer-by-layer approach (32), except in this case, the process happens in one pot and is controlled by electrostatics rather than sequential addition of materials with alternating charges.

Zwitterionic polymers have been previously shown to exhibit stealth capabilities (26, 33). Specifically, quaternary ammoniumcarboxylic acidterminated zwitterions have been used to successfully resist fouling in 50% fetal bovine serum (25). ILs offer a modular material that offers outstanding tunability of parameters. They, thus, offer an excellent addition to the available set of tools for controlling NP surface properties.

The NMR data show, through quantitative peak integration using tetramethylsilane, that despite adding a 1:2 ratio of cation:anion, the IL modifies the NP at an equal molar ratio of 1:1. When a 1:1 ratio is added in the case of choline hexenoate, the resulting coating is less able to resist the serum proteins, suggesting that the excess of anion confers a benefit when self-assembling around the PLGA core in the case of this anion.

The results of the in vitro serum test indicate that the PAIL-NPs outperform the conventional PEGylated particles. The primary mechanism of PEGs ability to resist serum proteins has been as attributed to its hydrophilicity. The data reported here suggest that the way in which PAILs protect the NP is more complex. Compared with the lead candidate anion (hexenoate), hexanoate has the same structure but lacks the double bond in the 2 position. This simple change in anion composition resulted in significantly reduced ability of the capped NPs to resist serum adsorption. The removal of this double bond has a marked effect on its ability to protect the NP from serum proteins, with the choline hexanoate particles increasing in size by 178.4% within 10 min. Comparatively, the lead candidate choline hexenoate 1:2 is able to resist any size change in pure serum up to 90 min. We hypothesize that the protein avoidance comes from poor solvation of the proteins, such that the proteins actively avoid interacting with the IL layering around the NP. Anions that contain oxygen atoms (other than the carboxylic acid functional group) performed significantly more poorly in capping ILs than those without additional oxygen atoms. This may be due to specific interactions occurring between the electronegative oxygen atoms and pockets of the proteins. Solvation of cytochrome c has previously been reported for choline dihydrogen phosphate by Forsyth et al. (34), where they hypothesize that its ability to act as both a hydrogen bond acceptor and donor enables its capacity to stabilize the protein, including its secondary structures.

At the conclusion of the serum test, the surface charge of the particles was measured. The bare particles showed neutralized surfaces, while both the PEGylated and PAIL-NPs retained negative zeta potentials of ca. 15 mV. The serum-exposed particles were then examined by SDS-PAGE after 2 and 20 min of exposure. Across all molecular weights, the PAIL-NPs show very faint or nonexistent bands, indicating that the PAIL-NPs have successfully lowered protein adsorption relative to the bare and PEG controls. This experiment was carried out by mixing the NPs with pure serum, which exposes the NPs to a very high concentration of protein, resulting in significant adsorption even in the case of the PEGylated particles.

The low levels of hemolysis of mouse RBCs in vitro (<10%) suggest that the PAIL-NPs do not induce cell lysis, which is an important factor in developing new agents delivered intravenously. More broadly, consideration of toxicity is critical when selecting ILs to screen, and as such, the components chosen to make the ILs were selected to ensure that they have high biocompatibility. The lead anion, trans-2-hexenoic acid, is on the Generally Regarded as Safe list and is used as a food additive to alter flavor and fragrance (35).

The in vivo testing of the NPs in healthy BALB/c mice showed that, once again, the PAIL-NPs outperformed both the PEGylated and bare controls, showing the greatest retention in the bloodstream of the mice at 24 hours. The use of PAIL-NPs instead of the control NPs resulted in a >2-fold reduction in inflammatory cytokine IL-6, suggesting the particles were far less immunostimulatory than the controls. In addition, the use of the PAIL coating substantially altered the BD of the particles, leading to a significant reduction in hepatic accumulation at 24 hours. Instead, 50% of the administered dose appeared in the lung tissue, with a lung:liver ratio of ca. 12 for the PAIL-NPs. Taking a closer look at RBCs removed from the mice 24 hours after injection using electron microscopy reveals the mechanism of this altered BD. RBCs examined from PAIL-NPtreated mice show both adhered NPs and shear marks on the surface of the RBC. No adherence is seen in RBCs removed from mice in the other treatment groups. When PAIL-NPs are exposed to RBCs in vitro, 50% of the NPs added appear attached to the surface of the RBCs. Our hypothesis for this phenomenon is that given the poor solvation of the serum proteins, the RBCs are the most abundant surface that the NP comes into contact with after injection. The precise mechanism for the interaction between the RBCs and the PAIL-NPs is yet to be uncovered, but a working hypothesis is that the terminal anionic layer of the PAIL-NPs interacts electrostatically with the abundant cationic lipids (namely, phosphatidylcholine and sphingomyelin, which are very structurally similar to the cation of the IL) in the outermost layer of RBCs. This kind of electrostatic interaction has been reported before in the case of negatively charged silica NPs, where the interaction of the NPs with RBC surfaces resulted in hemolysis (36). However, the alternating charge composition of the IL-NPs do not result in a high degree of hemolysis, perhaps because the cationic layer of IL is able to shield the terminal anionic layer, which prevents the IL-coated NP from entering the membrane to the point of rupture.

The data presented in Fig. 4 strongly suggest that PAIL-NPs attach to the surfaces of RBCs in the bloodstream after injection and are systemically circulated until they encounter the dense capillary beds, which shear the particles off into the endothelium of the surrounding blood vessels (37). When injected into the tail vein, the lung tissue is the first dense capillary bed encountered by circulating RBCs. This hitchhiking phenomenon has been reported previously (37), with two substantial differences. First, PAIL-NPs spontaneously adhere to the RBCs in the bloodstream, while previous methods required an ex vivo treatment to observe attachment. Second, the PAIL-NPs remain in the lung tissue at 50% of the injected dose at 24 hours and are not cleared by the RES (reticuloendothelial system), while previous hitchhiked NPs only showed preferential accumulation after 6 hours of administration.

The results presented here show the potential of ILs in enhancing the capabilities of NPs for drug delivery, especially given their large compositional diversity (11) and the high degree of tunability. Many exciting questions and possibilities need future attention, including understanding the specific interactions between the ILs and the proteins in the serum and the mechanisms of their interactions with the RBC surface. With further research focused on mechanisms and safety, IL-coated NPs open new opportunities in drug delivery.

Here, we report the first use of biocompatible ionic solvents as NP surface modifiers for reducing opsonization. Choline hexenoate emerged as the leading PAIL, stably attaching to the surface of PLGA particles. The PAIL-NPs showed excellent resistance to protein adsorption in vitro and, when administered in vivo, provided greater retention in the bloodstream compared with PEGylated and bare NPs. PAIL also substantially altered the BD of the NPs, with 50% of the administered dose accumulating in the lungs. Electron microscopy of RBCs at the conclusion of the experiment showed that this altered BD was a result of the PAIL-NPs spontaneously adhering to the RBCs in the bloodstream. Overall, we demonstrate the potential of the use of ILs as materials in NP drug delivery.

Choline bicarbonate, trans-2-hexenoic acid, acetonitrile [high-performance liquid chromatography (HPLC) grade, 99.8% purity], phosphate-buffered saline (PBS), D2O, Resomer RG 504 H, poly(d,l-lactide-co-glycolide) 50:50 (PLGA) with molecular weight (MW) 38,000 to 54,000 kDa and that was carboxylic acid terminated, PEG (MW 8000), and tetramethylsilane were obtained from Sigma-Aldrich (St. Louis, MO). DiD was obtained from Thermo Fisher Scientific.

Synthesis of ILs. Various carboxylic acids dissolved in ultrapure water were reacted with choline bicarbonate in a specified molar ratio (cation:carboxylic acid) at 40C for 12 hours. A rotary evaporator was then used to dry the resulting ILs at 20 mbar at 60C for 2 hours. The residual water was removed under a pressure of (760 mmHg) at 60C for 48 hours. 1H NMR characterization was performed and was found to be consistent with the previously published spectra (19).

NP core synthesis. PLGA was dissolved into HPLC-grade acetonitrile (ACN) at 1 mg/ml and vortexed for 5 min to ensure homogeneity. The far-red fluorescent dye DiD was then added into the PLGA/ACN organic phase solution at a concentration of ~1% (maximum capacity, 3%) by mass of PLGA. The final organic-phase solution was observed to turn a bright light-to-medium turquoise blue color after vortexing for another 5 min to suspend the DiD in the PLGA solution.

To synthesize uncapped PLGA NPs containing fluorescent DiD dye, 2 ml of the previously described organic-phase [(1 mg PLGA/1 ml ACN) with 1% by mass PLGA fluorescent dye] formulation was added slowly dropwise to the aqueous phase (3 ml of Milli-Q water or 3 ml of D2O for 1H NMR analysis) and allowed to stir in open air for 3 hours in the dark (38). After 3 hours of mixing in open air to achieve solvent evaporation, the uncapped NP solution was then removed from the magnetic stirring apparatus and stored in the dark at 4C in a 1.5-ml centrifuge tube.

Synthesis of PEG-capped PLGA NPs (PEG-PLGA-DiD NP). To synthesize PEG-capped PLGA NPs containing DiD dye, PEG was pre-added to the aqueous phase (3 ml of Milli-Q or D2O water) at a [2.5:1] PEG:PLGA mass/mass ratio between the PEG in the aqueous phase and PLGA in the added organic phase. This aqueous solution was left to mix for 30 min in open air in the dark via a magnetic stir bar in the round-bottom flask. Two milliliters of the previously described organic-phase PLGA formulation was then added slowly dropwise to the aqueous phase and allowed to stir in open air for 3 hours.

Synthesis of IL-capped PLGA NPs (PAIL-PLGA DiD NP). After the uncapped NPs were synthesized, they were stored in the dark in 1.5-ml centrifuge tubes at 4C for about 1 hour to stabilize before neat-synthesized IL was added all at once via pipette directly to the center vortex of a solution of uncapped NPs at a concentration of 10 mg neat IL/mg PLGA under magnetic stirring conditions in open air and allowed to mix for another 3 hours to allow for the PLGA surface self-assembly capping process.

NP filtration and storage. Both PEGylated and PAIL-modified NP solutions were then centrifuge filtered in Amicon Ultra-4 centrifugal filter units, 10K MWCO (Millipore, 4 ml) at 3000 rpm for 50 min to eliminate unbound IL or PEG (8 kDa) in the NP solution. The resultant filtered NPs were then washed in MilliQ, 1 PBS (pH 7.4), or D2O water and filtered at the same parameters. The final filtered NPs were then brought up to 1 ml in D2O or MQ-H2O for in vitro characterization. NPs were brought up to 1 ml with 1 PBS (pH 7.4) for in vitro physiological/biological work or 0.9% isotonic physiological saline for immediate use in vivo work and stored in the dark at 4C in 1.5-ml centrifuge tubes.

NMR spectroscopy. Spectra were recorded on an A600a Agilent DD2 600 MHz NMR spectrometer. Each sample contained 1000 l (2 mg) of NPs in D2O. Neat tetramethylsilane (TMS) was used additionally for quantitative NMR as an internal reference standard at a known amount of 4.5 mg (density = 0.648 g/ml at 25C, MW 88.22 g/mol).

DLS was performed on a Zetasizer ZEN3600 (Malvern, UK) in a disposable polystyrene cuvette (hydrodynamic radii) or DTS1070 (zeta potential) cell at 25C. Each sample (100 l) was diluted up to 1000 l (1:10) in H2O.

Quantification of fluorescence was achieved with a Spectramax i3 plate reader (Molecular Devices, San Jose, USA) using Corning Costar 96-well assay black and clear bottom plates (#3603) at excitation/emission wavelengths of 644 and 670 nm. A calibration curve was obtained by serial dilution with acetonitrile over a concentration range of 0.01 109 to 9.54 109 mg/ml. Each well contained 200 l. The experimental samples were measured in quadruplicate.TEM was performed via a Hitachi 7800 TEM at 80.0 kV using copper TEM grids (Electron Microscopy Sciences, carbon film 300 mesh copper). The samples were prepared by drop-casting a diluted NP solution (2 l/1 ml of MQ-H2O), negative staining with 2% uranyl acetate, and washing with MQ-H2O, and stored in a dry and dark TEM grid box for 24 hours.

NP size kinetics in neat mouse serum (by DLS). Disposable polystyrene cuvettes were used in a Malvern Zetasizer at 25C to monitor the size changes of the NPs in mouse serum. Control spectra were recorded both for the NPs at 1:10 dilution in MQ-H2O and neat mouse serum. One hundred microliters of surface-unmodified, PEG-coated, and IL-coated PLGA NP samples was separately diluted up to 1000 l (1:10) in neat whole commercial mouse serum (Invitrogen, #10410). Each samples size in serum was measured from 2 to 100 min and actively examined for any size shifts every ~4 to 6 min from the original control (MQ-H2O) peak population. This continued until the NP population peak in serum was observed to begin shifting toward 200+ nm from the original MQ-H2O NP reference peak, indicating the starting point of protein adsorption and protein corona formation.

NP zeta potential kinetics in neat mouse serum. NPs were diluted (100:1000 l) in whole normal mouse serum and incubated at 25C up until the terminal size point, with occasional gentle pipette aspiration and ejection to simulate in vivo flow conditions. To minimize damage to the gold electrode plates in the zeta potential cell by whole neat serum, centrifuge filtration was performed twice and the sample was reconstituted in 2 ml of MQ-H2O each time, as a modified protocol by Partikel et al. (30), at 1500 rpm for 15 min each (30 min total per sample) to gently flush through unbound serum proteins and preserve PLGA NP integrity. Each samples final filtrate was then brought up to 1 ml in MQ-H2O, and zeta potential values were respectively measured in cleaned and prepared zeta potential DTS1070 cells.

SDS-PAGE following incubation in neat mouse serum. NPs were mixed into whole normal mouse serum (200 l NPs:800 l neat serum) and incubated at 25C for two time points2 and 20 min. After treating with neat serum, each sample was centrifuged thrice for 15 min at 3000 rpm. After each centrifugation, 800 l of the upper nonadsorbed serum phase was carefully removed and replaced with an equivalent volume of 1 PBS (pH 7.4), thoroughly mixed by pipetting, and allowed to rest for 5 min. A final, fourth, centrifugation was performed for 10 min for each sample, after which the final NP sample was carefully isolated and transferred to a fresh tube. Laemmli buffer was added to each sample at a 1:1 ratio to each sample and subjected to a 100C degradation for 5 min. SDS-PAGE (12%, tris-Gly-SDS running buffer, 20-l loading, Bio-Rad) was then performed for 30 min at 200 V. The gel was washed three times for 5 min each in 200 ml of MQ-H2O. Water was removed, and the gel was covered with ready-to-use Coomassie stain and shaken slowly for an hour. The gel was briefly washed with MQ-H2O again and then destained with 50% HPLC methanol solution and 10% glacial acetic acid solution until the background was removed and the ladder/bands were clearly visible. Last, the gel was washed with MQ-H2O again to remove the excess destaining solution and then imaged using an iPhone camera.Kinetic hemolysis assays were performed using a modified protocol adapted from Evans et al. (39), in which 250 l of whole blood was exsanguinated from a wild-type adult BALB/c mouse 3 months of age immediately postmortem via CO2 induction and delivered into a K2-EDTAcoated vacutainer tube to prevent coagulation. Whole blood was then centrifuged at 1000g for 10 min, and then plasma was discarded to isolate the RBC pellet. The RBC pellet was then restored to 250 l with 1 PBS (pH 7.4) and centrifuged at 500g for 5 min. This wash was repeated twice more. Four hundred ninety microliters of 1 PBS (pH 7.4) was then pipetted into each of 4 ml 1.5 ml conical tubes. Washed isolated erythrocytes (10 l) were then added into each tube to produce a 1:50 dilution. These tubes constituted the stocks of diluted RBCs.

In a 96-well clear plate, each well received 20 l of control or NP solution + 180 l (1:10) of diluted RBC stock. The positive internal control was denoted as 20 l of 20% Triton X-100 into 180 l of diluted erythrocytes. The negative internal control was denoted as 1 PBS (pH 7.4) at the same dilution. The 96-well plate with samples was incubated at 37C for 1 hour and then centrifuged at 500g for 10 min. After centrifugation, 100 l of supernatant was collected and transferred from each treatment well into a new clear, flat-bottomed 96-well plate, which was then measured for peak absorbance at an experimentally determined 405 nm on a Spectramax i3 plate reader as a kinetic measurement over 2 hours at 25C. For analysis of data, the absorbance readings from 1 PBS (pH 7.4) negative internal control (0%) were used to subtract background measurement for all samples. From there, all quadruplicate measurements were normalized as a percentage of hemolysis to the Triton X-100 positive internal control (100%).

Animals. Female BALB/c mice (12 weeks of age) were purchased from Charles River Laboratories (MA, USA). All experiments were performed according to the approved protocols by the Institutional Animal Care and Use Committee of the Faculty of Arts and Sciences, Harvard University, Cambridge.

Healthy 3-month-old adult female BALB/c mice were used to evaluate pharmacokinetics (PK) and BD of the NPs. The study used the following four groups for BD and PK studies in healthy BALB/c mice: (i) ~70-nm spherical PLGA DiD particles (negative control), (ii) ~120-nm spherical PEG-PLGA DiD particles (positive control), (iii) ~180-nm spherical CAHA (Choline 2-hexenoate) 1:2 PLGA DiD particles, and (iv) 0.9% saline internal control injection. One hundred microliters of PLGA, PEG-PLGA, and CAHA 1:2-PLGA NPs in 0.9% physiological saline (final concentration, ~1 1012 NPs) was administered intravenously by tail vein injection in parallel for BD and PK purposes (n = 6). To perform pharmacokinetic studies, ~40 l of blood per mouse was taken from the submandibular vein without injection (0 min) and immediately after (within 2 min) injection, as well as at 1, 6, and 24 hours. Extracted aliquots of blood during the study were analyzed on a fluorescence plate reader to quantify the number of NPs in circulation as a percentage of the administered dose. To do this, blood extracted was directly delivered into K2-EDTAcoated tubes and immediately stored in the dark at 4C to efficiently preserve and quantify NP fluorescence.

After acquiring blood at the 24-hour time point, fluorescence for all samples time points was measured as described above. To quantify the relative percentage of NPs remaining in circulation after injection at each blood sample time point, the background fluorescence [relative fluorescence unit (RFU)] of untreated blood (time 0) was first subtracted from all blood samples at 2 min, 1 hour, 6 hours, and 24 hours. After background subtraction, the raw fluorescence (RFU) at 1, 6, and 24 hours were then compared to that of 2 min (100% fluorescence of administered dose) to obtain the percentage of NPs remaining in circulation after injection over time.

At the 24-hour terminal blood sampling time point, each mouse was exsanguinated under isoflurane anesthesia to collect final aliquots of blood for postmortem characterization [FACS, enzyme-linked immunosorbent assay (ELISA), and SEM] and then immediately euthanized by CO2 to collect main blood-filtering organs (heart, kidneys, lung, liver, spleen, and brain) for the BD study. Following modified and combined protocols originally from Oliveira et al. (40) and McGowan and Bidwell (41), a BD study was performed to measure the accumulation of the NPs in the organs. Immediately after extraction after euthanasia, organs were preserved within 50-l Falcon tubes in 4% methanol-free paraformaldehyde for 2 hours and then transferred to and washed several times in 1 PBS (pH 7.4). Immediately after washing in PBS, samples were then transferred to a petri dish, and IVIS small animal imaging was performed at 644 and 670 nm to visualize epifluorescence from the organs in units of radiant efficiency [(p/s/cm2/sr)/(W/cm2)]. IVIS imaging was performed not only to visualize the presence of fluorescent NPs but also to analyze the particle concentration in the organs.

After visualization by IVIS, organs for each treatment sample were submerged in 20-ml Falcon tubes in just enough radioimmunoprecipitation assay (RIPA) lysis buffer (RIPA Lysis and Extraction Buffer, G-Biosciences) to coat the surface of the tissue and homogenized at 30,000 rpm by the IKA handheld homogenizer (IKA Inc., T10 Basic S1, Ultra Turrax, 8000 to 30,000 rpm) until a homogeneous liquid was formed. After all treatment samples were homogenized, fluorescence (RFU) was quantified as described above. All data were analyzed using one-way ANOVA followed by post hoc Tukey.

Isolated RBCs from the 24-hour samples were analyzed by FACS to qualitatively evaluate whether the NPs were adhering to blood cells or being targeted by macrophages in plasma for clearance, if still in circulation at 24 hours. An in vitro assay was constructed first to examine feasibility of this theory before examining in vivo.

For in vitro studies, a 1:10 ratio of NPs/RBCs corresponding to in vivo injections was prepared by mixing each NP treatment with whole mouse blood. First, whole blood was exsanguinated from a wild-type control BALB/c mouse under inhalatory anesthesia for 10 min, combined with the NP treatments, and then centrifuged at 1000g for 10 min to obtain isolated RBCs. These RBCs were then washed using 1 PBS (pH 7.4) three times with centrifugation at 200g for 10 min between each wash. The final samples were each resuspended in 3 ml of 1 PBS (pH 7.4).

For in vivo samples, a representative mouse from the PLGA-DiD, saline, and CAHA 1:2-PLGA-DiD NP treatment groups was selected for examination after 24 hours (blood withdrawal and euthanasia). RBCs were isolated from whole blood withdrawn from each mouse and washed three times in 1 PBS (pH 7.4) as previously described. In addition, supernatant was collected and examined as well for macrophage NP uptake activity. All in vitro and in vivo samples underwent FACS analysis on an LSR II Fortessa flow cytometry machine to examine the detection and location of any NPs (which emitted far-red fluorescence from encapsulated DiD dye) at 670 nm.

After FACS confirmed the presence of NPs adhering onto RBCs both in vitro and in vivo, SEM was performed on these same RBC samples on a Supra55 SEM machine according to the previously established protocol of Brenner et al. (37)

Sera derived from whole blood taken from the final 24-hour in vivo time point after intravenous injection were analyzed using protocol accompanying an ELISA kit to detect IL-6. To conduct the ELISA, 100 l of serum from each treatment group was taken to establish the IL-6 response (Invitrogen Mouse IL-6 Uncoated ELISA Kit with protocol). Absorbance was measured at 450 nm on a 96-well clear ELISA plate using a Spectramax plate reader (Spectramax i3). After acquisition, 4PL statistical fitting was applied to the ELISA mouse IL-6 standard curve, and two-tailed paired t test of the means was applied to assess significance between two treatment groups at a time.

Statistical analyses were conducted using Microsoft Excel 2016 for PK (n = 6) and BD (n = 6) data, which were both analyzed using one-way ANOVA followed by Tukey post hoc test and two-tailed paired t test of the means when interested in cross-verifying significance between two treatment groups. Background buffer autofluorescence was subtracted from all fluorescence-related measurements to account for true sample values. Fluorescence (RFU) was quantified by a SpectraMax i3 plate reader on 200 l of homogenates at the same settings as prior to measure the percentage of NPs relative to the tail vein injection dose. 4PL statistical fitting via RStudio OpenSource was applied to the ELISA mouse IL-6 standard curve, and two-tailed paired t test of the means was applied to assess significance between two treatment groups at a time. All data are presented as means standard error of the mean. DLS is represented as a measure of intensity (%) for size or count for zeta potential. As an internal control, all DLS readings were measured with at least two internal readings/sample/trial. N, P, and statistical tests performed for each experiment are available in its respective figure caption in the text.

Acknowledgments: We thank J. Kim and D. Pan for the training on tail vein intravenous injections for in vivo experiments, M. Nurunnabi for the IVIS training, and D. Pan for the mouse blood for ex vivo experiments. We also thank Z. Zhao and P. Angsantikul for advice and input during the development of the in vivo and ex vivo experiments. We additionally thank the Harvard Center for Nanoscale Systems (CNS) for guidance in experimental development of electron microscopy imaging techniques, the Harvard Bauer Core for usage of flow cytometry instrumentation, and the Wyss Institute for usage of the DLS. We thank M. Goetz, S. D. Pedigo, and R. M. Wadkins for assistance with the SDS-PAGE experiments. Funding: This work was supported by funding from the John A. Paulson School of Engineering and Harvard University and the Sigma Xi Honor Society Student GIAR program. Author contributions: E.E.L.T. conceived the idea. S.M. and E.E.L.T. developed the idea. S.M., C.M.H., and E.E.L.T. developed the experiments. C.M.H. and E.E.L.T. performed the experiments. C.M.H. and E.E.L.T. analyzed the data. E.E.L.T. wrote the paper, with contributions and critical revisions from all coauthors. Competing interests: E.E.L.T. and S.M. are inventors on an invention that covers some aspects of the technology reported in this manuscript (owned and managed by Harvard University). S.M. is a shareholder/consultant/board member of Liquideon LLC, CAGE Bio, and i2O Therapeutics. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Protein-avoidant ionic liquid (PAIL)coated nanoparticles to increase bloodstream circulation and drive biodistribution - Science Advances

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New Class of Drugs Harnesses Gold Nanocrystals to Heal and Protect the Brain – BioSpace

Clene Chief Executive Officer Rob Etherington. Photo courtesy of Clene.

Clene Nanomedicine is trying to set a new gold standard in neurodegenerative diseases through the development of a new class of drugs called bioenergetic nanotherapeutics that harnesses the properties of gold nanocrystals.

The gold nanocrystals are used to amplify bioenergetic reactions in patients in order to drive intracellular biological reactions. Bioenergetic nanotherapeutics are a clean break from pharmaceutical drug development that uses classical synthetic chemistry, Clene Chief Executive Officer Rob Etherington told BioSpace in an interview. Clenes lead asset is CNM-Au8, a bioenergetic nanocatalyst under development as an add-on treatment for neurodegenerative diseases like Parkinsons disease, multiple sclerosis and Amyotrophic Lateral Sclerosis (ALS). CNM-Au8 is designed to catalyze bio cellular reactions, and so far the company has seen the asset live up to its promise in clinical studies. The companys gold nanocrystals are grown in water and patients drink the asset down. Research has so far indicated that Clene and its golden asset could become a pioneer in therapeutic neurorepair and neuroprotection.

To date, CNM-Au8 has demonstrated safety in Phase I studies, remyelination and neuroprotective effects in preclinical models and is currently being assessed in a Phase II study for the treatment of chronic optic neuropathy in patients with multiple sclerosis. Additionally, CNM-Au8 is being studies in Phase II and Phase III studies for disease progression in patients with ALS. In September, Clene presented interim results from the REPAIR-MS and REPAIR-PD Phase II studies demonstrating the effects of its lead nanocatalytic therapeutic, CNM-Au8. The preliminary data demonstrate CNM-Au8-mediated modulation of key brain bioenergetic metabolites in relapsing multiple sclerosis (MS) and Parkinson's disease (PD) patients. Data from the studies indicate catalytic bioenergetic improvements across important CNS bioenergetic metabolites, including total nicotinamide adenine dinucleotide (NAD) levels, NAD+/NADH ratio, and adenosine triphosphate (ATP) levels, indicating a homeostatic effect of CNM-Au8 on brain bioenergetics, the company said.

Etherington said the data from the REPAIR-MS and REPAIR-PD studies indicate that CNM-Au8 is working mechanistically to address a foundational challenge common to many neurodegenerative diseases, which is that stressed or failing neurons need additional energy to survive and repair.

We now have insights that CNM-Au8 is driving bioenergetics within the brain, which is a foundational insight for the further development of Clene's neurorepair clinical programs, Etherington said. He added that should the data from the interim analysis pan out, it indicated that CNM-Au8 could effectively benefit millions of people across the globe suffering from multiple sclerosis and other neurodegenerative diseases.

There are multiple drugs already on the market for these neurodegenerative diseases. CNM-Au8 is not meant to replace those drugs, but to work alongside them. Etherington explained that CNM-Au8 is not designed to target a specific protein, nor it is designed to block or antagonize something, like most drugs. Rather, Clenes compound is designed to enhance the intracellular biological actions necessary to repair and reverse neuronal damage, Etherington said.

We are purposely seeking to reverse neurodegernation. We want to let the cell take care of its own housekeeping and enhance whats naturally occurring in the central nervous system, he said.

Etherington acknowledged the concept of drinking bits of gold nanocrystals may sound like something out of a Star Trek episode, but insisted the idea is sound. Gold-salt injections were historically used to treat rheumatoid arthritis decades ago, but were dropped due to health concerns. Clene had the idea to build a stable, oral nanotherapeutic, so they could see less toxicity and drive bioenergetics targets for a suite of neurodegenerative diseases, he said.

Its so out of the box that it can be a bit mind boggling. Were breaking with the traditional path and shifting the paradigm to how we think neurodegenerative disease should be treated, he said.

Not only is Clene moving forward in its clinical assessment of CNM-Au8, the company is planning to go public with a special purpose acquisition companies (SPAC) merger before the end of 2020. 2020 has been the busiest year for this kind of stock entry, with a 250% surge. As BioSpace recently reported, there have been nearly two dozen SPAC mergers in the biotech sector this year, targeting more than $3.5 billion in proceeds. When the company goes public, Etherington said Clenes management team will remain the same and the funding raised from this reverse stock merger will provide the finances that can support the companys ongoing research.

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New Class of Drugs Harnesses Gold Nanocrystals to Heal and Protect the Brain - BioSpace

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Nanomedicine Market is Expected to Thrive at Impressive CAGR by 2026 & Top Key Players are Combimatrix, Ablynx, Abraxis Bioscience, Celgene,…

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Nanomedicine Market is Expected to Thrive at Impressive CAGR by 2026 & Top Key Players are Combimatrix, Ablynx, Abraxis Bioscience, Celgene,...

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2020 Report: Growth Opportunities in Gene Therapy, Automated Bioanalytics, and Biomarker Platforms – ResearchAndMarkets.com – Business Wire

DUBLIN--(BUSINESS WIRE)--The "Growth Opportunities in Gene Therapy, Automated Bioanalytics, and Biomarker Platforms" report has been added to ResearchAndMarkets.com's offering.

The research provides technological insights across inflammation, infectious diseases, and microbiomics.

The Life Science, Health & Wellness TOE will feature disruptive technology advances in the global life sciences industry. The technologies and innovations profiled will encompass developments across genetic engineering, drug discovery and development, biomarkers, tissue engineering, synthetic biology, microbiome, disease management, as well as health and wellness among several other platforms.

The Health & Wellness cluster tracks developments in a myriad of areas including genetic engineering, regenerative medicine, drug discovery and development, nanomedicine, nutrition, cosmetic procedures, pain and disease management and therapies, drug delivery, personalized medicine, and smart healthcare.

Innovations in Life Sciences, Health & Wellness from:

For more information about this report visit https://www.researchandmarkets.com/r/tkufmb

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Iran ranks third for top researchers in Islamic world 2020 – Tehran Times

TEHRAN Iran ranked third for the highly cited researchers in the world among Islamic countries in 2020, according to the recently published report of Highly Cited Researchers by Web of Science.

Among the world's top researchers, 13 Islamic countries are listed, which hold a share of 3 percent (2.85%) among the world's top researchers.

Saudi Arabia with 120 researchers, Malaysia with 17, Iran with 12, and Turkey with 11 researchers have the highest number of highly cited researchers among Islamic countries.

To be included in the list of top researchers, all scientific activities over the last 10 years are evaluated at the international level, including the number of articles, number of citations, number of highly cited articles, number of citations to highly cited articles, as well as issues such as observing ethical principles in research.

So, approximately 6,389 researchers have been selected as highly cited researchers in 2020.

From Iran in 2020, similar to 2019, 12 top researchers have been included in the list of 6,389 top-cited researchers in the world.

The country's top researchers have been in the cross-field (6 people), agricultural sciences (2 people), mathematics (2 people), and engineering (2 people), respectively.

The United States is home to the highest number of Highly Cited Researchers, with 2,650 authors, representing 41.5 percent of the researchers on the list. China, home to 770 researchers is the second country has the highest concentration of Highly Cited Researchers in the world. The United Kingdom is also a hotbed of talent, with 514 authors, and Germany, Australia, Canada, the Netherlands, and France are all home to over 150 researchers each.

Top scientific articles

Iran's share of the world's top scientific articles is 3 percent, Gholam Hossein Rahimi Sheerbaf, the deputy science minister, said in October.

The countrys share in the whole publications worldwide is 2 percent, he noted, highlighting, for the first three consecutive years, Iran has been ranked first in terms of quantity and quality of articles among Islamic countries.

Iranian articles rank 16 and 15 in Web of Science and Scopus, respectively.

The Journal Citation Reports 2019 ranking includes 42 journals from Iran, including the Journal of Nanostructure in Chemistry with an impact factor of 4.077.

Iranian scientific journals such as the Journal of Nanostructures (affiliated to Kashan University), Nanomedicine Journal (Mashhad University of Medical Sciences), Journal of Nanoanalysis (Tehran University of Medical Sciences) were listed in the ESCI index of WOS database.

Moreover, the Journal of Water and Environmental Nanotechnology, Nanomedicine Research Journal, and International Nanoscience and Nanotechnology were also listed in the Scopus Index.

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Iran ranks third for top researchers in Islamic world 2020 - Tehran Times

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Nanomedicine Market Shares, Strategies and Forecast Worldwide, 2017 to 2023 – The Haitian-Caribbean News Network

Overview:

Nanomedicineis an offshoot of nanotechnology, and refers to highly-specific medical intervention at the molecular scale for curing diseases or repairing damaged tissues. Nanomedicine uses nano-sized tools for the diagnosis, prevention and treatment of disease, and to gain increased understanding of the complex underlying pathophysiology of the disease. It involves three nanotechnology areas of diagnosis, imaging agents, and drug delivery with nanoparticles in the 11,000 nm range, biochips, and polymer therapeutics.

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Majority of nanomedicines prescribedcurrently, allow oral drug delivery and its demand is increasing significantly. Although these nanovectors are designed to translocate across the gastrointestinal tract, lung, and bloodbrain barrier, the amount of drug transferred to the organ is lower than 1%; therefore improvements are challenging. Nanomedicines are designed to maximize the benefit/risk ratio, and their toxicity must be evaluated not only by sufficiently long term in vitro and in vivo studies, but also pass multiple clinical studies.

Market Analysis:

The Global Nanomedicine Market is estimated to witness a CAGR of 17.1% during the forecast period 20172023. The nanomedicine market is analyzed based on two segments therapeutic applications and regions.

The major drivers of the nanomedicine market include its application in various therapeutic areas, increasing R&D studies about nanorobots in this segment, and significant investments in clinical trials by the government as well as private sector. The Oncology segment is the major therapeutic area for nanomedicine application, which comprised more than 35% of the total market share in 2016. A major focus in this segment is expected to drive the growth of the nanomedicine market in the future.

Regional Analysis:

The regions covered in the report are the Americas, Europe, Asia Pacific, and Rest of the World (ROW). The Americas is set to be the leading region for the nanomedicine market growth followed by Europe. The Asia Pacific and ROW are set to be the emerging regions. Japan is set to be the most attractive destination and in Africa, the popularity and the usage of various nano-drugs are expected to increase in the coming years. The major countries covered in this report are the US, Germany, Japan, and Others.

Therapeutic Application Analysis:

Nanomedicines are used as fluorescent markers for diagnostic and screening purposes. Moreover, nanomedicines are introducing new therapeutic opportunities for a large number of agents that cannot be used effectively as conventional oral formulations due to poor bioavailability. The therapeutic areas for nanomedicine application are Oncology, Cardiovascular, Neurology, Anti-inflammatory, Anti-infectives, and various other areas. Globally, the industry players are focusing significantly on R&D to gain approval for various clinical trials for future nano-drugs to be commercially available in the market. The FDA should be relatively prepared for some of the earliest and most basic applications of nanomedicine in areas such as gene therapy and tissue engineering. The more advanced applications of nanomedicine will pose unique challenges in terms of classification and maintenance of scientific expertise.

Key Players:

Merck & Co. Inc., Hoffmann-La Roche Ltd., Gilead Sciences Inc., Novartis AG, Amgen Inc., Pfizer Inc., Eli Lilly and Company, Sanofi, Nanobiotix SA, UCB SA and other predominate & niche players.

Competitive Analysis:

At present, the nanomedicine market is at a nascent stage but, a lot of new players are entering the market as it holds huge business opportunities. Especially, big players along with the collaboration with other SMBs for clinical trials of nanoparticles and compounds are coming with new commercial targeted drugs in the market and they are expecting a double-digit growth in the upcoming years. Significant investments in R&D in this market are expected to increase and collaborations, merger & acquisition activities are expected to continue.

Benefits:

The report provides complete details about the usage and adoption rate of nanomedicines in various therapeutic verticals and regions. With that, key stakeholders can know about the major trends, drivers, investments, vertical players initiatives, government initiatives towards the nanomedicine adoption in the upcoming years along with the details of commercial drugs available in the market. Moreover, the report provides details about the major challenges that are going to impact on the market growth. Additionally, the report gives the complete details about the key business opportunities to key stakeholders to expand their business and capture the revenue in the specific verticals to analyze before investing or expanding the business in this market.

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Nanomedicine Market Shares, Strategies and Forecast Worldwide, 2017 to 2023 - The Haitian-Caribbean News Network

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Healthcare Nanotechnology Market Overview with Detailed Analysis, Competitive landscape, Forecast to 2026| Amgen, Teva Pharmaceuticals, Abbott – The…

The global Healthcare Nanotechnology market is broadly analyzed in this report that sheds light on critical aspects such as the vendor landscape, competitive strategies, market dynamics, and regional analysis. The report helps readers to clearly understand the current and future status of the global Healthcare Nanotechnology market. The research study comes out as a compilation of useful guidelines for players to secure a position of strength in the global Healthcare Nanotechnology market. The authors of the report profile leading companies of the global Healthcare Nanotechnology market, such as Amgen, Teva Pharmaceuticals, Abbott, UCB, Roche, Celgene, Sanofi, Merck & Co, Biogen, Stryker, Gilead Sciences, Pfizer, 3M Company, Johnson & Johnson, Smith & Nephew, Leadiant Biosciences, Kyowa Hakko Kirin, Shire, Ipsen, Endo International They provide details about important activities of leading players in the competitive landscape.

The report predicts the size of the global Healthcare Nanotechnology market in terms of value and volume for the forecast period 2019-2026. As per the analysis provided in the report, the global Healthcare Nanotechnology market is expected to rise at a CAGR of XX % between 2019 and 2026 to reach a valuation of US$ XX million/billion by the end of 2026. In 2018, the global Healthcare Nanotechnology market attained a valuation of US$_ million/billion. The market researchers deeply analyze the global Healthcare Nanotechnology industry landscape and the future prospects it is anticipated to create.

This publication includes key segmentations of the global Healthcare Nanotechnology market on the basis of product, application, and geography (country/region). Each segment included in the report is studied in relation to different factors such as consumption, market share, value, growth rate, and production.

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The comparative results provided in the report allow readers to understand the difference between players and how they are competing against each other. The research study gives a detailed view of current and future trends and opportunities of the global Healthcare Nanotechnology market. Market dynamics such as drivers and restraints are explained in the most detailed and easiest manner possible with the use of tables and graphs. Interested parties are expected to find important recommendations to improve their business in the global Healthcare Nanotechnology market.

Readers can understand the overall profitability margin and sales volume of various products studied in the report. The report also provides the forecasted as well as historical annual growth rate and market share of the products offered in the global Healthcare Nanotechnology market. The study on end-use application of products helps to understand the market growth of the products in terms of sales.

Global Healthcare Nanotechnology Market by Product: Nanomedicine, Nano Medical Devices, Nano Diagnosis, Others, Nanomedicine has the highest percentage of revenue by type, with more than 86% in 2019.

Global Healthcare Nanotechnology Market by Application: , Anticancer, CNS Product, Anti-infective, Others, According to the application, anticancer and CNS products accounted for 17.56% and 22.70% of the market in 2019 respectively.

The report also focuses on the geographical analysis of the global Healthcare Nanotechnology market, where important regions and countries are studied in great detail.

Global Healthcare Nanotechnology Market by Geography:

Methodology

Our analysts have created the report with the use of advanced primary and secondary research methodologies.

As part of primary research, they have conducted interviews with important industry leaders and focused on market understanding and competitive analysis by reviewing relevant documents, press releases, annual reports, and key products.

For secondary research, they have taken into account the statistical data from agencies, trade associations, and government websites, internet sources, technical writings, and recent trade information.

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Key questions answered in the report:

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Table Of Contents:

1 Market Overview of Healthcare Nanotechnology1.1 Healthcare Nanotechnology Market Overview1.1.1 Healthcare Nanotechnology Product Scope1.1.2 Market Status and Outlook1.2 Global Healthcare Nanotechnology Market Size Overview by Region 2015 VS 2020 VS 20261.3 Global Healthcare Nanotechnology Market Size by Region (2015-2026)1.4 Global Healthcare Nanotechnology Historic Market Size by Region (2015-2020)1.5 Global Healthcare Nanotechnology Market Size Forecast by Region (2021-2026)1.6 Key Regions, Healthcare Nanotechnology Market Size YoY Growth (2015-2026)1.6.1 North America Healthcare Nanotechnology Market Size YoY Growth (2015-2026)1.6.2 Europe Healthcare Nanotechnology Market Size YoY Growth (2015-2026)1.6.3 Asia-Pacific Healthcare Nanotechnology Market Size YoY Growth (2015-2026)1.6.4 Latin America Healthcare Nanotechnology Market Size YoY Growth (2015-2026)1.6.5 Middle East & Africa Healthcare Nanotechnology Market Size YoY Growth (2015-2026) 2 Healthcare Nanotechnology Market Overview by Type2.1 Global Healthcare Nanotechnology Market Size by Type: 2015 VS 2020 VS 20262.2 Global Healthcare Nanotechnology Historic Market Size by Type (2015-2020)2.3 Global Healthcare Nanotechnology Forecasted Market Size by Type (2021-2026)2.4 Nanomedicine2.5 Nano Medical Devices2.6 Nano Diagnosis2.7 Others 3 Healthcare Nanotechnology Market Overview by Application3.1 Global Healthcare Nanotechnology Market Size by Application: 2015 VS 2020 VS 20263.2 Global Healthcare Nanotechnology Historic Market Size by Application (2015-2020)3.3 Global Healthcare Nanotechnology Forecasted Market Size by Application (2021-2026)3.4 Anticancer3.5 CNS Product3.6 Anti-infective3.7 Others 4 Global Healthcare Nanotechnology Competition Analysis by Players4.1 Global Healthcare Nanotechnology Market Size by Players (2015-2020)4.2 Global Top Manufacturers by Company Type (Tier 1, Tier 2 and Tier 3) (based on the Revenue in Healthcare Nanotechnology as of 2019)4.3 Date of Key Manufacturers Enter into Healthcare Nanotechnology Market4.4 Global Top Players Healthcare Nanotechnology Headquarters and Area Served4.5 Key Players Healthcare Nanotechnology Product Solution and Service4.6 Competitive Status4.6.1 Healthcare Nanotechnology Market Concentration Rate4.6.2 Mergers & Acquisitions, Expansion Plans 5 Company (Top Players) Profiles and Key Data5.1 Amgen5.1.1 Amgen Profile5.1.2 Amgen Main Business5.1.3 Amgen Healthcare Nanotechnology Products, Services and Solutions5.1.4 Amgen Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.1.5 Amgen Recent Developments5.2 Teva Pharmaceuticals5.2.1 Teva Pharmaceuticals Profile5.2.2 Teva Pharmaceuticals Main Business5.2.3 Teva Pharmaceuticals Healthcare Nanotechnology Products, Services and Solutions5.2.4 Teva Pharmaceuticals Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.2.5 Teva Pharmaceuticals Recent Developments5.3 Abbott5.5.1 Abbott Profile5.3.2 Abbott Main Business5.3.3 Abbott Healthcare Nanotechnology Products, Services and Solutions5.3.4 Abbott Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.3.5 UCB Recent Developments5.4 UCB5.4.1 UCB Profile5.4.2 UCB Main Business5.4.3 UCB Healthcare Nanotechnology Products, Services and Solutions5.4.4 UCB Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.4.5 UCB Recent Developments5.5 Roche5.5.1 Roche Profile5.5.2 Roche Main Business5.5.3 Roche Healthcare Nanotechnology Products, Services and Solutions5.5.4 Roche Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.5.5 Roche Recent Developments5.6 Celgene5.6.1 Celgene Profile5.6.2 Celgene Main Business5.6.3 Celgene Healthcare Nanotechnology Products, Services and Solutions5.6.4 Celgene Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.6.5 Celgene Recent Developments5.7 Sanofi5.7.1 Sanofi Profile5.7.2 Sanofi Main Business5.7.3 Sanofi Healthcare Nanotechnology Products, Services and Solutions5.7.4 Sanofi Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.7.5 Sanofi Recent Developments5.8 Merck & Co5.8.1 Merck & Co Profile5.8.2 Merck & Co Main Business5.8.3 Merck & Co Healthcare Nanotechnology Products, Services and Solutions5.8.4 Merck & Co Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.8.5 Merck & Co Recent Developments5.9 Biogen5.9.1 Biogen Profile5.9.2 Biogen Main Business5.9.3 Biogen Healthcare Nanotechnology Products, Services and Solutions5.9.4 Biogen Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.9.5 Biogen Recent Developments5.10 Stryker5.10.1 Stryker Profile5.10.2 Stryker Main Business5.10.3 Stryker Healthcare Nanotechnology Products, Services and Solutions5.10.4 Stryker Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.10.5 Stryker Recent Developments5.11 Gilead Sciences5.11.1 Gilead Sciences Profile5.11.2 Gilead Sciences Main Business5.11.3 Gilead Sciences Healthcare Nanotechnology Products, Services and Solutions5.11.4 Gilead Sciences Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.11.5 Gilead Sciences Recent Developments5.12 Pfizer5.12.1 Pfizer Profile5.12.2 Pfizer Main Business5.12.3 Pfizer Healthcare Nanotechnology Products, Services and Solutions5.12.4 Pfizer Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.12.5 Pfizer Recent Developments5.13 3M Company5.13.1 3M Company Profile5.13.2 3M Company Main Business5.13.3 3M Company Healthcare Nanotechnology Products, Services and Solutions5.13.4 3M Company Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.13.5 3M Company Recent Developments5.14 Johnson & Johnson5.14.1 Johnson & Johnson Profile5.14.2 Johnson & Johnson Main Business5.14.3 Johnson & Johnson Healthcare Nanotechnology Products, Services and Solutions5.14.4 Johnson & Johnson Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.14.5 Johnson & Johnson Recent Developments5.15 Smith & Nephew5.15.1 Smith & Nephew Profile5.15.2 Smith & Nephew Main Business5.15.3 Smith & Nephew Healthcare Nanotechnology Products, Services and Solutions5.15.4 Smith & Nephew Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.15.5 Smith & Nephew Recent Developments5.16 Leadiant Biosciences5.16.1 Leadiant Biosciences Profile5.16.2 Leadiant Biosciences Main Business5.16.3 Leadiant Biosciences Healthcare Nanotechnology Products, Services and Solutions5.16.4 Leadiant Biosciences Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.16.5 Leadiant Biosciences Recent Developments5.17 Kyowa Hakko Kirin5.17.1 Kyowa Hakko Kirin Profile5.17.2 Kyowa Hakko Kirin Main Business5.17.3 Kyowa Hakko Kirin Healthcare Nanotechnology Products, Services and Solutions5.17.4 Kyowa Hakko Kirin Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.17.5 Kyowa Hakko Kirin Recent Developments5.18 Shire5.18.1 Shire Profile5.18.2 Shire Main Business5.18.3 Shire Healthcare Nanotechnology Products, Services and Solutions5.18.4 Shire Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.18.5 Shire Recent Developments5.19 Ipsen5.19.1 Ipsen Profile5.19.2 Ipsen Main Business5.19.3 Ipsen Healthcare Nanotechnology Products, Services and Solutions5.19.4 Ipsen Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.19.5 Ipsen Recent Developments5.20 Endo International5.20.1 Endo International Profile5.20.2 Endo International Main Business5.20.3 Endo International Healthcare Nanotechnology Products, Services and Solutions5.20.4 Endo International Healthcare Nanotechnology Revenue (US$ Million) & (2015-2020)5.20.5 Endo International Recent Developments 6 North America6.1 North America Healthcare Nanotechnology Market Size by Country6.2 United States6.3 Canada 7 Europe7.1 Europe Healthcare Nanotechnology Market Size by Country7.2 Germany7.3 France7.4 U.K.7.5 Italy7.6 Russia7.7 Nordic7.8 Rest of Europe 8 Asia-Pacific8.1 Asia-Pacific Healthcare Nanotechnology Market Size by Region8.2 China8.3 Japan8.4 South Korea8.5 Southeast Asia8.6 India8.7 Australia8.8 Rest of Asia-Pacific 9 Latin America9.1 Latin America Healthcare Nanotechnology Market Size by Country9.2 Mexico9.3 Brazil9.4 Rest of Latin America 10 Middle East & Africa10.1 Middle East & Africa Healthcare Nanotechnology Market Size by Country10.2 Turkey10.3 Saudi Arabia10.4 UAE10.5 Rest of Middle East & Africa 11 Healthcare Nanotechnology Market Dynamics11.1 Industry Trends11.2 Market Drivers11.3 Market Challenges11.4 Market Restraints 12 Research Finding /Conclusion 13 Methodology and Data Source 13.1 Methodology/Research Approach13.1.1 Research Programs/Design13.1.2 Market Size Estimation13.1.3 Market Breakdown and Data Triangulation13.2 Data Source13.2.1 Secondary Sources13.2.2 Primary Sources13.3 Disclaimer13.4 Author List

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