Preparation and characterisation of thermoresponsive poly [(N-isopropylacrylamide-co-acrylamide-co(hydroxyethyl acrylate)] microspheres as a matrix for the pulsed release of drugs

Despite the large number of publications and patents concerning the pH/thermoresponsive polymers, few data are available concerning the preparation of thermoresponsive crosslinked microspheres from preformed polymers. Therefore, N-isopropylacrylamide-co-acrylamide-co-2-hydroxyethylacrylate copolymers were obtained as a new thermoresponsive material with a lower critical solution temperature (LCST) around 36 °C, in phosphate buffer at pH=7.4, and with a crosslinkable OH group in their structure. The LCST value was determined both by UV spectroscopy and microcalorimetric analysis. These copolymers were solubilised in acidified aqueous solution below their LCST, dispersed in mineral oil and transformed in stable microspheres by crosslinking with glutaraldehyde. The thermoresponsive microspheres were characterised by optical and scanning electron microscopy, swelling degree and water retention. The pore dimensions of microspheres and the retention volumes of some usually drugs and typical compounds were evaluated at different temperatures by liquid chromatography. Indomethacin, as a model drug, was included in microspheres by the solvent evaporation method. Finally, the influence of temperature and of temperature cycling on drug release was investigated.