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.