Degradable disulfide core-cross-linked micelles as a drug delivery system prepared from vinyl functionalized nucleosides via the RAFT process

Biomacromolecules. 2008 Nov;9(11):3321-31. doi: 10.1021/bm800867n. Epub 2008 Oct 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Survival
  • Chlorocebus aethiops
  • Disulfides / chemistry*
  • Drug Delivery Systems*
  • Micelles*
  • Nucleosides / chemistry*
  • Polymers / chemical synthesis*
  • Polymers / pharmacokinetics
  • Riboflavin / administration & dosage
  • Vinyl Compounds / chemistry*

Substances

  • Disulfides
  • Micelles
  • Nucleosides
  • Polymers
  • Vinyl Compounds
  • Riboflavin