title: Immunosafety and chronic toxicity evaluation of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) polymer micelles for paclitaxel delivery.
abstract: To investigate the physicochemical properties, immunosafety and chronic toxicity of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance (H-NMR), dynamic light scattering and fluorescence probe technique were conducted to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded polymeric micelles were characterized regarding their particle size, entrapment efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The complement activation in human serum and mast cells degranulation were performed by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60) micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w. Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60) micelles have spherical shape with dense core. In vitro release study showed a sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60) showed a lower complement activation ability compared to mPEG-PLA (50/50) and CremophorÂ® EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG-PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and Cr EL.
authors.affiliation: a Department of Pharmaceutics, State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: a Department of Pharmaceutics, State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: a Department of Pharmaceutics, State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , China.
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Sun
authors.affiliation: a Department of Pharmaceutics, State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , China.
authors.forename: Nihad
authors.initials: N
authors.lastname: Cheraga
authors.affiliation: a Department of Pharmaceutics, State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Tu
mesh_terms: D000818:Animals; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D046529:Microscopy, Electron, Transmission / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage* / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects*; D011108:Polymers / Q000008:administration & dosage* / Q000009:adverse effects*; D011817:Rabbits
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Complement activation; mPEG-PLA; mast cell degranulation; paclitaxel; pseudoallergy