Degradable disulfide core-cross-linked micelles as a drug delivery system prepared from vinyl functionalized nucleosides via the RAFT process.
A nucleosides containing block copolymer, poly(polyethylene glycol methyl ether methacrylate)- block-poly(5'-O-methacryloyluridine) (PPEGMEMA 30- b-PMAU 80) was self-assembled in aqueous medium and cross-linked via RAFT polymerization at 60 degrees C to afford core-cross-linked micelles exhibiting a PPEGMEMA corona and a polynucleotide core. A disulfide cross-linking agent, bis(2-methacryloyloxyethyl)disulfide, was employed to cross-link the structure via the RAFT process resulting in core-shell nanoparticles, which can degrade under reductive conditions. The resulting core-cross-linked micelles readily hydrolyzed into free block copolymers in the presence of dithiothreitol (DTT) in less than 1 h, depending on the concentration of the reducing agent and the amount of cross-linker in the micelle. A small fraction of permanently cross-linked micelle was found as the result of conventional chain transfer to disulfide containing compounds. A model drug, vitamin B 2, was loaded into the micelle. The loading capacity increased with increasing cross-linking degree. The amount of drug released reached 60-70% after 7 h in the presence of DTT (0.65 mM), while the cross-linked micelle in the absence of dithiothreitol shows only a delayed drug release. Cytotoxicity tests confirmed the biocompatibility of the polymers and the residues after reduction.
Zhang
Ling
L
Centre for Advanced Macromolecular Design, School of Chemical Sciences and Engineering, The University of New South Wales, Sydney NSW 2052, Australia.
Liu
Wenguang
W
Lin
Lin
L
Chen
Dayong
D
Stenzel
Martina H
MH
D000818:Animals; D019556:COS Cells; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004220:Disulfides / Q000737:chemistry*; D016503:Drug Delivery Systems; D008823:Micelles; D009705:Nucleosides / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012256:Riboflavin / Q000008:administration & dosage; D014753:Vinyl Compounds / Q000737:chemistry*
D004220:Disulfides; D008823:Micelles; D009705:Nucleosides; D011108:Polymers; D014753:Vinyl Compounds; D012256:Riboflavin