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

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• 作者：Gheorghe Fundueanu^a ; ^b ; ^{ghefun@icmpp.ro} ; Marieta Constantin^a ; Ionela Oanea^a ; Valeria Harabagiu^a ; Paolo Ascenzi^c ; Bogdan C. Simionescu^a ; ^d
• 关键词：Drug delivery system ; Lower critical solution temperature ; pH/thermoresponsive copolymers ; Smart polymers ; Inverse size exclusion chromatography
• 刊名：Acta Biomaterialia
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：8
• 期：3
• 页码：1281-1289
• 全文大小：898 K

文摘

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^?, 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.