Poly(vinyl alcohol) microspheres with pH- and thermosensitive properties as temperature-controlled drug delivery

Gheorghe Fundueanu, Marieta Constantin, Paolo Ascenzi

Research output: Contribution to journalArticlepeer-review


One of the most important inconveniences of the pH- and temperature-sensitive hydrogels is the loss of thermosensitivity when relatively large amounts of a pH-sensitive monomer are co-polymerized with N-isopropylacrylamide (NIPAAm). In order to overcome this drawback, we propose here a method to prepare thermosensitive poly(vinyl alcohol) (PVA) microspheres with a higher content of carboxylic groups that preserve thermosensitive properties. Moreover, PVA possesses excellent mechanical properties, biocompatibility and non-toxicity. PVA microspheres were obtained by suspension cross-linking of an acidified aqueous solution of the polymer with glutaraldehyde. Poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (poly(NIPAAm-co-HMAAm)), designed to have a lower critical solution temperature (LCST) corresponding to that of the human body, was grafted onto PVA microspheres in order to confer them with thermosensitivity. Then, the pH-sensitive functional groups (COOH) were introduced by reaction between the un-grafted OH groups of PVA and succinic anhydride. The pH- and temperature-sensitive PVA microspheres display a sharp volume transition under physiological conditions around the LCST of the linear polymer. The microspheres possess good drug-loading capacity without losing their thermosensitive properties. Under simulated physiological conditions, the release of drugs is controlled by temperature.

Original languageEnglish
Pages (from-to)3899-3907
Number of pages9
JournalActa Biomaterialia
Issue number10
Publication statusPublished - Oct 2010


  • Drug delivery
  • Intelligent microspheres
  • Lower critical solution temperature
  • pH- and temperature-sensitive co-polymers
  • Poly(vinyl alcohol)

ASJC Scopus subject areas

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


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