prediction of the appropriate size of drug molecules that could be released by a pulsatile mechanism from ph/thermoresponsive microspheres obtained from preformed polymers

preparation of cross-linked ph/thermoresponsive microspheres from preformed polymers is still lacking in literature since copolymers possessing both temperature- and ph-sensitive units together with a cross-linkable moiety in appropriate ratios are required. moreover, choosing of the appropriate drugs able to be loaded and then released in a pulsatile manner is randomly performed. here, we report the synthesis of ph/thermoresponsive cross-linked microspheres based on n-isopropylacrylamide andn-alloc-ethylenediamine. a chromatographic method was developed to predict the appropriate size of drug molecules that could be loaded and then released in a pulsatile manner. accordingly, it was established that common drugs (salicylic acid, benzoic acid, nicotinic acid, lidocaine and diclofenac), with molecular weights ranging between 100 and 1000 g mol⁻¹, could be loaded and released in a pulsatile manner. biologic molecules with higher molecular weights (heparin, lysozyme and bovine serum albumin) are completely excluded from the pores of cross-linked ph/thermoresponsive microspheres both below and above the volume phase transition temperature.