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

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. (C) 2010 Acta Materialia Inc Published by Elsevier Ltd All rights reserved