Poly(N-isopropylacrylamide-co-hydroxyethylacrylamide) thermosensitive microspheres: The size of microgels dictates the pulsatile release mechanism

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• 作者：Gheorghe Fundueanu ; Marieta Constantin ; Ionela Asmar ; ei ; S ; a Bucatariu ; Valeria Harabagiu ; Paolo Ascenzi ; Bogdan C. Simionescu
• 关键词：AIBN ; N ; N&prime ; -azobisisobutyronitrile ; CP ; cloud point ; DSC ; differential scanning calorimetry ; ESEM ; environmental scanning electron microscopy ; GA ; glutaraldehyde ; HEAAm ; N-hydroxyethylacrylamide ; LCST ; lower critical solution temperature ; Mn ; number-average molecular weight ; Mw ; weight-average molecular weight ; NIPAAm ; N-isopropylacrylamide ; PB ; phosphate buffer ; PI ; polydispersity index ; poly(NIPAAm) ; poly(N-isopropylacrylamide) ; poly(NIPAAm-co-HEAAm) ; poly(N-isopropylacrylamide-co-N-hydro
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：November, 2013
• 年：2013
• 卷：85
• 期：3_part_PA
• 页码：614-623
• 全文大小：1930 K

文摘

Poly(N-isopropylacrylamide-co-N-hydroxyethylacrylamide) (poly(NIPAAm-co-HEAAm)) was prepared as a new thermosensitive copolymer possessing a sharp phase transition around the human body temperature. The effect of the copolymer concentration on the lower critical solution temperature (LCST) was determined under physiological conditions by cloud point (CP) and differential scanning calorimetric (DSC) methods. Then, thermosensitive microspheres were prepared from preformed copolymers by chemical cross-linking of hydroxyl groups with glutaraldehyde at a temperature situated slightly below LCST of the copolymer solution. The volume phase transition temperature (VPTT) of corresponding cross-linked microspheres was determined from swelling degree-temperature curve. The microspheres were loaded with model drug indomethacin by the solvent evaporation method. The DSC analysis proved that the drug is molecularly dispersed in the polymer network. Finally, the influence of the microsphere size on drug release was investigated. It was established that microspheres with the diameter ranging between 5 and 60 渭m release the drug with almost the same rate below (in the swollen state) and above the VPTT (in the collapsed state). On the contrary, microspheres with the diameter ranging between 125 and 220 渭m release a significantly higher amount of indomethacin below than above the VPTT. This different behavior is enough to assure a pulsatile release mechanism when the temperature changes cyclically below and above the VPTT. However, both small and large microspheres release a large amount of the drug during the collapsing process.