alexa Doxorubicin-loaded PLGA nanoparticles by nanoprecipitation: preparation, characterization and in vitro evaluation.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Betancourt T, Brown B, BrannonPeppas L

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Abstract AIMS: The lack of specificity of chemotherapeutic agents to cancer tissue commonly leads to dose-limiting side effects and poor therapeutic results. Drug delivery systems promise to improve the deficiencies of chemotherapeutic treatment by modifying the biodistribution and pharmacokinetics of the drug in vivo. Here, we report the preparation, characterization and in vitro evaluation of a carrier for the chemotherapeutic drug doxorubicin based on acid-capped poly(lactic-co-glycolic acid) nanoparticles. METHODS: Doxorubicin-loaded nanoparticles were prepared by nanoprecipitation with bovine serum albumin as the stabilizer. Nanoparticles were characterized and their interaction with MDA-MB-231 breast cancer cells was examined with confocal microscopy and a toxicological assay. RESULTS: Spherical particles with an average diameter of 230 nm, a zeta-potential of -45 mV and a maximum drug loading of 5 wt\% were prepared. Doxorubicin was found to be quickly released at endolysosomal pH of 4.0 but was released at a slower rate at pH 7.4. Nanoparticles were found to deliver the drug into cells quickly and in higher quantity than when presented in solution and were found to result in a therapeutic efficacy comparable to the free drug. DISCUSSION: Nanoprecipitation was found to be a promising method for the preparation of nanoparticles with relatively high doxorubicin loading. The pH-dependent release behavior is discussed to possibly be a result of accelerated degradation of the polymer and decreasing ionic interaction between the drug and the polymer at acidic pH. Additional studies are needed to determine why increased nuclear localization of the drug when delivered in the form of nanoparticles did not result in increased therapeutic efficacy in vitro. CONCLUSION: Nanoparticles formulated by nanoprecipitation of acid-ended poly(lactic-co-glycolic acid) were found to be able to control the release of doxorubicin in a pH-dependent manner and to effectively deliver high payloads of the drug in an active form to MDA-MB-231 breast cancer cells. This article was published in Nanomedicine (Lond) and referenced in Journal of Nanomedicine & Nanotechnology

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