title: Fabrication and reduction-sensitive behavior of polyion complex nano-micelles based on PEG-conjugated polymer containing disulfide bonds as a potential carrier of anti-tumor paclitaxel.
abstract: This work is aimed at the development of a reduction-sensitive drug carrier for the delivery of the anti-cancer drug paclitaxel (PTX). N,N'-bis(acryloyl)cystamine (CBA) was reacted with ethanolamine (AEOL) via Michael addition to synthesize cationic poly(CBA-AEOL) (PCA) containing disulfide bonds. Subsequently, polycaprolactone (PCL) was grafted from PCA to form a novel reduction-sensitive copolymer (PCA-g-PCL). The PCA-g-PCL copolymer self-assembled as spherical micelles with a mean size of ca. 108nm. The disulfide bonds in the PCA-g-PCL copolymer contributed to the reduction-sensitivity of the micelles, observed as stepwise aggregation under simulated reduction conditions. To improve the stability of PCA-g-PCL micelles in aqueous media, carboxyl-terminated poly(ethylene glycol) methyl ether (mPEG-COOH) was conjugated with the PCA-g-PCL copolymer via electrostatic interaction to produce polyion complex micelles with a hydrophilic PEG surface. The in vitro release of PTX from the mPEG@PCA-g-PCL micelle showed a reduction sensitive profile, namely the rate of drug release strongly depended upon the concentration of the reducing agent. Leakage of PTX was limited to below 30% under normal conditions while almost all the drug was released in 9h under reduction conditions with 40mM DTT. In conclusion, the assembled mPEG@PCA-g-PCL micelle with reduction-sensitive controlled release shows great potential for improving the therapeutic effect of paclitaxel.
authors.affiliation: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Huang
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiahui
authors.initials: J
authors.lastname: Yu
authors.forename: Junping
authors.initials: J
authors.lastname: Zeng
authors.forename: Peter R
authors.initials: PR
authors.lastname: Chang
authors.forename: Haibo
authors.initials: H
authors.lastname: Xu
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D008823:Micelles; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D004337:Drug Carriers; D007477:Ions; D008823:Micelles; D011108:Polymers; D017239:Paclitaxel