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.
Centre for Advanced Macromolecular Design, School of Chemical Sciences and Engineering, The University of New South Wales, Sydney NSW 2052, Australia.
Ling
L
Zhang
Wenguang
W
Liu
Lin
L
Lin
Dayong
D
Chen
Martina H
MH
Stenzel
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