Biocompatible thermoresponsive PEGMA nanoparticles crosslinked with cleavable disulfide-based crosslinker for dual drug release

J Biomed Mater Res A. 2015 Jan;103(1):243-51. doi: 10.1002/jbm.a.35146. Epub 2014 Apr 3.

Abstract

Smart materials have been attracting much attention because of their stimuli responsive nature. We have synthesized biocompatible thermoresponsive crosslinked poly(ethylene glycol) methyl ether methacrylate (PEGMA)-co-vinyl pyrrolidone nanoparticles (PEGMA NPs) using disulfide-based crosslinker by surfactant-free emulsion polymerization method. Particle characterization studies were carried out by dynamic light scattering, and scanning electron microscopy. Polymerization kinetics, effect of crosslinker and initiator concentrations on both average hydrodynamic diameter and polydispersity index were investigated. Hydrodynamic diameters of thermoresponsive PEGMA NPs were decreased from 210 nm to 90 nm upon heating over the lowest critical solution temperature (LCST). Disulfide crosslinked PEGMA NPs were demonstrated as a dual delivery system. Rhodamine B, a model of small-sized drug molecule, and poly(ethylene glycol) (PEG)-alizarin yellow, a model of large drug molecule, were loaded into PEGMA NPs where LCST of these NPs was tuned to 37°C, the body temperature. The rhodamine B was released from PEGMA NPs upon heating to 39°C. Then, PEG-alizarin content was released by subsequent degradation of nanoparticles using dithiothreitol (DTT), which reduces disulfide bonds to thiols. Furthermore, cytotoxicity studies of PEGMA NPs were carried out in 3T3 cells, which resulted in no toxic effect on the cells.

Keywords: disulfide-based crosslinker; drug delivery; poly ethylene glycol methyl ether methacrylate; stimuli-responsive nanoparticles; surfactant-free emulsion polymerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials*
  • Disulfides / chemistry*
  • Drug Carriers*
  • Methacrylates / chemistry*
  • Microscopy, Electron, Scanning
  • Nanoparticles*
  • Polyethylene Glycols / chemistry*

Substances

  • Biocompatible Materials
  • Disulfides
  • Drug Carriers
  • Methacrylates
  • polyethylene glycol methacrylate
  • Polyethylene Glycols