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      Nanoparticle-Mediated Pulmonary Drug Delivery: A Review

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          Abstract

          Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed.

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          Nanoparticles for drug delivery to the lungs.

          The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. Incorporating therapeutics with polymeric nanoparticles offers additional degrees of manipulation for delivery systems, providing sustained release and the ability to target specific cells and organs. However, nanoparticle delivery to the lungs has many challenges including formulation instability due to particle-particle interactions and poor delivery efficiency due to exhalation of low-inertia nanoparticles. Thus, novel methods formulating nanoparticles into the form of micron-scale dry powders have been developed. These carrier particles exhibit improved handling and delivery, while releasing nanoparticles upon deposition in the lungs. This review covers the development of nanoparticle formulations for pulmonary delivery as both individual nanoparticles and encapsulated within carrier particles.
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            Development of Nanoparticles for Antimicrobial Drug Delivery

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              Chitosan nanoparticles: preparation, size evolution and stability.

              Characterisation of chitosan-tripolyphosphate nanoparticles is presented with the aim of correlating particle shape and morphology, size distribution, surface chemistry, and production automatisation with preparation procedure, chitosan molecular weight and loaded protein. Nanoparticles were prepared by adding drop wise a tripolyphosphate-pentasodium solution to chitosan solutions under stirring. Trehalose, mannitol and polyethylene-glycol as bioprotectants were used to prevent particle aggregation and to reduce mechanical stress during freezing and drying processes. As a novel result, time evolution of the particle size distribution curve showed the presence of a bimodal population composed of a fraction of small particles and of a second fraction of larger particles attributed to the rearrangement of particles after the addition of tripolyphosphate. Storage for 4 weeks resulted in a slight increase in average size, due to the continuous rearrangement of small particles. Improvement of nanoparticle stability after lyophilisation and spray-drying was observed in the presence of all bioprotectants. Trehalose was the best protectant for both methods. Finally, in vivo tests using chick embryos assessed the biocompatibility of chitosan, tripolyphosphate and the nanoparticles. The simple ionotropic gelation method with low-MW chitosan was effective in achieving reproducible nanoparticles with the desired physico-chemical and safety characteristics. Copyright © 2013 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                April 2014
                08 April 2014
                : 15
                : 4
                : 5852-5873
                Affiliations
                Institute for Pharmaceutical Technology, TU Braunschweig, Mendelssohnstr. 1, 38106 Braunschweig, Germany; E-Mail: mukta.paranjpe@ 123456tu-bs.de
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: c.mueller-goymann@ 123456tu-bs.de ; Tel.: +49-531-391-5650; Fax: +49-531-391-8108.
                Article
                ijms-15-05852
                10.3390/ijms15045852
                4013600
                24717409
                f8a5b593-7c93-4bd2-94b1-cb2630651c7e
                © 2014 by the authors; licensee MDPI, Basel, Switzerland

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 22 January 2014
                : 28 March 2014
                : 28 March 2014
                Categories
                Review

                Molecular biology
                nanoparticles,sln,toxicity,lung cell models,aerosol,nebulization,lung disease
                Molecular biology
                nanoparticles, sln, toxicity, lung cell models, aerosol, nebulization, lung disease

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