Park, Jason and Fong, Peter M. and Lu, Jing and Russell, Kerry S. and Booth, Carmen J. and Saltzman, W. Mark and Fahmy, Tarek M. (2009) PEGylated PLGA nanoparticles for the improved delivery of doxorubicin. Nanomedicine: Nanotechnology, Biology and Medicine, 5 (4). 410 - 418.
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Official URL: http://www.sciencedirect.com/science/article/B7MDB...
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 ~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.
|Uncontrolled Keywords:||Doxorubicin; PLGA; PEGylated; Nanoparticle; Drug delivery|
|Subjects:||Biomedical Science > Nanomedicine|
|Deposited On:||22 Apr 2010 11:05|
|Last Modified:||22 Apr 2010 11:05|
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