title: Selective tissue distribution and long circulation endowed by paclitaxel loaded PEGylated poly(ε-caprolactone-co-L-lactide) micelles leading to improved anti-tumor effects and low systematic toxicity.
abstract: High tumor targeting and sustained drug concentration are key points for successful anti-tumor therapy, however, it is a challenging task. In this work, a novel micelle formulation of paclitaxel (PTX) has been prepared for the purpose of prolonging the blood circulation time as well as improving the accumulation of the drug within the tumor tissue. PEGylated P(CL-co-LLA) (poly(ε-caprolactone-co-L-lactide)) micelles containing PTX were prepared by solid dispersion-sonication method with a higher drug-loading efficiency and encapsulation ratio (28.4% and 94.7%, respectively). Pharmacokinetic study revealed that the drug-loading micelles exhibited a higher AUC values and a prolonged residence time of drug in the blood circulation than those of PTX injection. As demonstrated by tissue distribution and anti-tumor study in S180 tumor-bearing mice, the PEG-P(CL-co-LLA)/PTX micelles displayed modified tissue distribution of PTX and increased accumulation of PTX in tumor, therefore, resulted in anti-tumor effects enhancement and drug concentration in the normal tissues reduction. Furthermore, the preliminary safety tests were performed by measuring the body weight, histopathology, blood cell counts and clinical chemistry parameters, and the results showed no subacute toxicity to hematological system, major organs or tissues in mice. Taken together, our valuation shows that PEG-P(CL-co-LLA) micelles is a potential drug delivery system of PTX for the effective treatment of the tumor and systematic toxicity reduction, thus, the micellar formulation can provide a useful alternative dosage form for i.v. administration of PTX.
authors: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China; Shanghai Institute of Pharmaceutical Industry, 1111 Zhongshan beiyi Road, Shanghai 200437, PR China.
authors: Feihu
authors: F
authors: Wang
authors: Yuanyuan
authors: Y
authors: Shen
authors: Xiaofen
authors: X
authors: Xu
authors: Li
authors: L
authors: Lv
authors: Yanggong
authors: Y
authors: Li
authors: Jieying
authors: J
authors: Liu
authors: Min
authors: M
authors: Li
authors: Aijie
authors: A
authors: Guo
authors: Shengrong
authors: S
authors: Guo
authors: Fang
authors: F
authors: Jin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; C062968:lactide-caprolactone copolymer; D017239:Paclitaxel
keywords: Anti-tumor; In vivo toxicity; PEG-P(CL-co-LLA); Paclitaxel; Tissue distribution