title: Synthesis and characterization of multi-functional linear-dendritic block copolymer for intracellular delivery of antitumor drugs.
abstract: A novel amphiphilic linear-dendritic block copolymer, semi-polyamidoamine-b-poly(D,L-lactic acid) (PALA) was synthesized and evaluated for its potential as a drug delivery system in this study. PALA was self-assembled in aqueous solution to form nanomicelles with low critical micelle concentration; antitumor drug docetaxel (DTX) was successfully encapsulated into micelles. The prepared micelles demonstrated pH-induced charge conversion and dimension changes. In vitro drug release suggested susceptibility of DTX-loaded micelles to acidic microenvironment. Hemolysis and cytotoxicity testing also indicated in vitro biocompatibility of PALA. Pharmacokinetic study in rats proved that DTX-loaded PALA micelles enhanced the AUC of DTX and prolonged drug clearance in comparison to conventional DTX injection (Taxotere(®)). It was concluded that self-assembled micelles from linear-dendritic block copolymer PALA demonstrated potential for intracellular delivery of anticancer molecules, and that its safety and efficacy in chemotherapy should be further studied.
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Qiao
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Qineng
authors.initials: Q
authors.lastname: Ping
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry*; D000077143:Docetaxel; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D008823:Micelles; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D008823:Micelles; C104700:PAMAM Starburst; D011091:Polyesters; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D019344:Lactic Acid; C033616:poly(lactide)