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首页> 外文期刊>European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fuer Pharmazeutische Verfahrenstechnik e.V >Poly(N-isopropylacrylamide-co-hydroxyethylacrylamide) thermosensitive microspheres: The size of microgels dictates the pulsatile release mechanism
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Poly(N-isopropylacrylamide-co-hydroxyethylacrylamide) thermosensitive microspheres: The size of microgels dictates the pulsatile release mechanism

机译：聚（N-异丙基丙烯酰胺-共羟乙基丙烯酰胺）热敏微球：微凝胶的大小决定了脉动释放机制

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摘要

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 μm 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 μm 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.
机译：制备了聚（N-异丙基丙烯酰胺-共-N-羟乙基丙烯酰胺）（聚（NIPAAm-共-HEAAm）），作为一种新型的热敏共聚物，在人体温度附近具有明显的相变。在浊点（CP）和差示扫描量热法（DSC）方法下，在生理条件下确定共聚物浓度对较低的临界溶液温度（LCST）的影响。然后，通过在稍低于共聚物溶液的LCST的温度下通过羟基与戊二醛的化学交联，由预制的共聚物制备热敏性微球。由溶胀度-温度曲线确定相应的交联微球的体积相变温度（VPTT）。通过溶剂蒸发法在微球上装载了模型药物消炎痛。 DSC分析证明该药物分子分散在聚合物网络中。最后，研究了微球尺寸对药物释放的影响。已经确定，直径在5至60μm之间的微球以低于（溶胀状态）和高于VPTT（崩解状态）的速率释放药物。相反，直径在125至220μm之间的微球在VPTT下方释放的消炎痛明显高于VPTT。当温度在VPTT上下变化时，这种不同的行为足以确保脉动释放机制。但是，无论是大的还是小的微球，在崩解过程中都会释放出大量的药物。

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