4.5 Article

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

Journal

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 103, Issue 1, Pages 243-251

Publisher

WILEY
DOI: 10.1002/jbm.a.35146

Keywords

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

Funding

  1. Marie Curie International Reintegration [PIRG-GA-2009-256514]
  2. Selcuk University Scientific Research Fund [12201077]
  3. Scientific and Technological Research Council of Turkey [112M096, COST TD1004]

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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 degrees C, the body temperature. The rhodamine B was released from PEGMA NPs upon heating to 39 degrees 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. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 243-251, 2015.

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