Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) - Pluronic(®) F127 copolymers for controlled protein release

Int J Pharm. 2014 Jan 1;459(1-2):1-9. doi: 10.1016/j.ijpharm.2013.11.030. Epub 2013 Dec 4.

Abstract

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez(®) AN, GZ) and Pluronic(®) F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.

Keywords: Controlled release; Pluronics; Polyanhydride; Protein; Thermosensitive hydrogels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Cell Survival / drug effects
  • Chromatography, Gel
  • Delayed-Action Preparations
  • Differential Thermal Analysis
  • Drug Carriers
  • Female
  • Hydrogels / chemistry*
  • Hydrogels / toxicity
  • Kinetics
  • Macrophages / drug effects
  • Magnetic Resonance Spectroscopy
  • Maleates / chemistry*
  • Materials Testing
  • Poloxamer / chemistry*
  • Polymers
  • Polyvinyls / chemistry*
  • Proteins / administration & dosage*
  • Proteins / chemistry*
  • Rats
  • Rats, Wistar
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Viscosity
  • X-Ray Diffraction

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Maleates
  • Polymers
  • Polyvinyls
  • Proteins
  • polyvinylmethoxyethylene-maleic anhydride copolymer
  • Poloxamer