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      Preparation and characterization of poly(dl-lactide-co-glycolide) nanoparticles for siRNA delivery

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      International Journal of Pharmaceutics
      Elsevier BV

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          Abstract

          Synthetic short interfering RNA (siRNA) is promising for specific and efficient knockdown of disease-related genes. However, in vivo application of siRNA requires an effective delivery system. Commonly used siRNA carriers are based on polycations, which form electrostatic complexes with siRNA. Such poly- or lipoplexes are of limited use in vivo due to severe problems associated with toxicity, serum instability and non-specific immune-responses. The aim of the present study was to prepare uniformly sized nanoparticles (NPs) with a high load of siRNA by use of the safe and biodegradable poly-(DL-lactide-co-glycolide) (PLGA) polymer without including polycations. The siRNA was encapsulated in the core of NPs by the double emulsion solvent evaporation method. To optimize the NP formulation, the effects of important formulation and processing parameters were investigated systematically. Generally, spherical siRNA-loaded NPs (<300 nm, PDI<0.2, zeta potential -40 mV) were obtained. An encapsulation efficiency of up to 57% was achieved by adjusting the inner water phase volume, the PLGA concentration, the first emulsification sonication time, and stabilization of the water-oil interface with serum albumin. The integrity of siRNA was preserved during the preparation. Preparation of core-loaded siRNA-NPs based on PLGA and no cationic excipient seems possible and promising for delivery of siRNA. Copyright 2009. Published by Elsevier B.V.

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          Author and article information

          Journal
          International Journal of Pharmaceutics
          International Journal of Pharmaceutics
          Elsevier BV
          03785173
          May 2010
          May 2010
          : 390
          : 1
          : 70-75
          Article
          10.1016/j.ijpharm.2009.10.023
          19836438
          fea74c32-ee24-4d5d-986e-921f97205d2c
          © 2010

          https://www.elsevier.com/tdm/userlicense/1.0/

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