Poly(N-isopropylacrylamide-co-acrylamide) cross-linked thermoresponsive microspheres obtained from preformed polymers: Influence of the physico-chemical characteristics of drugs on their release profiles

Gheorghe Fundueanu, Marieta Constantin, Paolo Ascenzi

Research output: Contribution to journalArticlepeer-review

Abstract

Poly(N-isopropylacrylamide-co-acrylamide) copolymer was synthesized as an interesting thermoresponsive material possessing a phase transition temperature of around 36 °C in phosphate buffer, pH 7.4 (PB); the concentration was 10%, w/v. The copolymer maintains a sharp phase transition at a relatively high percentage of acrylamide. The lower critical solution temperature (LCST) of the copolymer is influenced by the concentration of copolymer solution in PB. The copolymer was transformed in thermoresponsive microspheres by chemical cross-linking of amide groups with glutaraldehyde. The key factors for the successful preparation of microspheres are the use of a concentrated polymer solution, a temperature (38 °C) that is high enough but lower than LCST, and a long reaction time (48 h). The microspheres were characterized by optical and scanning electron microscopy, swelling/deswelling kinetics, swelling degree, and PB retention at different temperatures. Finally, the influence of hydrophilicity/hydrophobicity and the molecular weight of the drugs (propranolol, lidocaine, vitamin B12) on their release profile from thermoresponsive microspheres were examined. Above LCST the hydrogel matrix is in the dehydrated state and hydrophobic interactions between the hydrophobic drugs and the polymer occur, modulating the release rate of the drugs. For hydrophilic drugs, the release rate is modulated mainly by the steric interaction between the drug molecule and the matrix.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalActa Biomaterialia
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • Drug delivery
  • Equilibrium swelling ratio
  • Intelligent microspheres
  • Lower critical solution temperature
  • pH/thermoresponsive copolymers

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Molecular Biology
  • Biomedical Engineering
  • Biomaterials

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