title: Reduction-Sensitive Polymeric Micelles Based on Docetaxel-Polymer Conjugates Via Disulfide Linker for Efficient Cancer Therapy.
abstract: In this article, the low-molecular weight biodegradable methoxy poly (ethylene glycol)-poly (D,L-lactide-co-glycolide) (PP) is chosen as polymeric skeleton to be conjugated with docetaxel (DTX) by disulfide bond (PP-SS-DTX) to construct the reduction-sensitive drug delivery system. The conjugates are synthesized via three steps and are further employed to physically load free DTX to develop the PP-SS-DTX/DTX micelles which exhibit many merits including high drug loading content, good stability, and stimuli-sensitive release of drugs. The hydrodynamic diameter of PP-SS-DTX/DTX micelles determined by DLS is 112.3 nm. The hemolysis assay reveals the good blood compatibility of PP-SS-DTX/DTX micelles. In order to investigate the reductive sensitivity of PP-SS-DTX/DTX micelles, dithiothreitol (DTT) is added into the release medium and a programmed drug release mode is observed in the conjugated micelles. In vitro cytotoxity assay shows that the PP-SS-DTX/DTX micelles are more cytotoxic than that of free DTX solution for both MCF-7 and B16F10 cancer cells. In addition, the PP-SS-DTX/DTX micelles also show a higher cellular uptake rate than that of free DTX. Hence, the prepared reduction-sensitive PP-SS-DTX/DTX micelles are effective on inhibiting cancer cells compared with the free DTX which would be a promising carrier in cancer therapy.
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province, 250012, P. R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province, 250012, P. R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Hospital of Traditional Chinese Medicine of Jimo, Shandong Province, P. R. China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province, 250012, P. R. China.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province, 250012, P. R. China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Luan
mesh_terms: D000818:Animals; D004220:Disulfides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel