Journal
DRUG DEVELOPMENT RESEARCH
Volume 70, Issue 7, Pages 512-519Publisher
WILEY
DOI: 10.1002/ddr.20322
Keywords
nanoparticle; carboxy-polyethylene glycol-poly(DL-lactic acid) block copolymer; camptothecin; biodistribution; drug release
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Carboxy-polyethylene glycol-poly(DL-lactic acid) block copolymer was synthesized by reductive amination of carboxy-polyethylene glycol-amine and aldehyde-ended poly(DL-lactic acid). The obtained product, PA-PEG-CB, composed of pure carboxy-polyethylene glycol-poly(DL-lactic acid) block copolymer and poly(DL-lactic acid), was used to prepare nanoparticles loaded with camptothecin (CPT), designated CPT-NP. CPT-NP with 500-600nm and approximately 1% (w/w) drug content were obtained by emulsification/evaporation, while nanoparticles with a drug content of only less than 0.1% (w/w) were prepared by dialysis. CPT-NP produced by emulsification/evaporation were used for in vitro and in vivo studies. CPT-NP released CPT gradually in phosphate-buffered saline, pH 7.4, at 37 degrees C over 48 h. Biodistribution profiles were compared between CPT-NP and CPT solution after i.v. injection into mice bearing sarcoma 180 solid tumor. CPT-NP retained CPT approximately 10 times more in plasma during the initial 8 h than CPT solution. The tumor level of CPT was more than 10 times higher with CPT-NP for the observation period (24 h), though the CPT concentration in the liver and spleen was much higher with CPT-NP. CPT-NP may be useful for tumor localization of CPT. Drug Dev Res 70: 512-519, 2009. (C) 2009 Wiley-Liss, Inc.
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