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Preparation of carboxy‐PEG‐PLA nanoparticles loaded with camptothecin and their body distribution in solid tumor–bearing mice

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 500–600 nm 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°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. © 2009 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Development Research Wiley

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