title: Prediction of the appropriate size of drug molecules that could be released by a pulsatile mechanism from pH/thermoresponsive microspheres obtained from preformed polymers.
abstract: 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 and N-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.
authors.affiliation: Department of Bioactive and Biocompatible Polymers, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iassy, Romania. ghefun@icmpp.ro
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Fundueanu
authors.forename: Marieta
authors.initials: M
authors.lastname: Constantin
authors.forename: Ionela
authors.initials: I
authors.lastname: Oanea
authors.forename: Valeria
authors.initials: V
authors.lastname: Harabagiu
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Bogdan C
authors.initials: BC
authors.lastname: Simionescu
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005029:Ethylenediamines / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D016062:Porosity
chemical_list: D000178:Acrylamides; D003692:Delayed-Action Preparations; D005029:Ethylenediamines; C031234:ethylenediamine; C067295:N-isopropylacrylamide