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      PEGylated PLGA nanoparticles for the improved delivery of doxorubicin

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          Abstract

          We hypothesize that the efficacy of doxorubicin (DOX) can be maximized and dose-limiting cardiotoxicity minimized by controlled release from PEGylated nanoparticles. To test this hypothesis, a unique surface modification technique was used to create PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating DOX. An avidin-biotin coupling system was used to control poly(ethylene glycol) conjugation to the surface of PLGA nanoparticles, of diameter approximately 130 nm, loaded with DOX to 5% (wt/wt). Encapsulation in nanoparticles did not compromise the efficacy of DOX; drug-loaded nanoparticles were found to be at least as potent as free DOX against A20 murine B-cell lymphoma cells in culture and of comparable efficacy against subcutaneously implanted tumors. Cardiotoxicity in mice as measured by echocardiography, serum creatine phosphokinase (CPK), and histopathology was reduced for DOX-loaded nanoparticles as compared with free DOX. Administration of 18 mg/kg of free DOX induced a sevenfold increase in CPK levels and significant decreases in left ventricular fractional shortening over control animals, whereas nanoparticle-encapsulated DOX produced none of these pathological changes. The efficacy of doxorubicin (DOX) may be maximized and dose-limiting cardiotoxicity minimized by controlled release from PEGylated nanoparticles. Administration of 18 mg/kg of free DOX induced a sevenfold increase in CPK levels and significant decreases in left ventricular fractional shortening in mice, whereas nanoparticle-encapsulated DOX produced none of these pathological changes.

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          Author and article information

          Journal
          Nanomedicine: Nanotechnology, Biology and Medicine
          Nanomedicine: Nanotechnology, Biology and Medicine
          Elsevier BV
          15499634
          December 2009
          December 2009
          : 5
          : 4
          : 410-418
          Article
          10.1016/j.nano.2009.02.002
          2789916
          19341815
          © 2009

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