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采用微流控方法合成的壳聚糖-硅氧烷杂化微球的表征及降解研究

Characterization and degradation study of chitosan-siloxane hybrid microspheres synthesized using a microfluidic approach.

作者信息

Cruz-Neves Susana, Shirosaki Yuki, Miyazaki Toshiki, Hayakawa Satoshi

机构信息

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0196, Japan.

Graduate School of Engineering, Kyushu Institute of Technology, 1-1 Sensui-cho, Tobata-ku, Kitakyushu, Fukuoka 804-8550, Japan.

出版信息

Mater Sci Eng C Mater Biol Appl. 2017 Dec 1;81:571-579. doi: 10.1016/j.msec.2017.08.035. Epub 2017 Aug 12.

Abstract

Chitosan microspheres can address challenges associated with poor bioavailability or unsustained drug release when used as drug delivery systems thanks to their mucoadhesiveness, which allows the drug dosage to be retained in the gastrointestinal track for extended periods. Chitosan-3-glycidoxypropyltrimethoxysilane-β-glycerophosphate (chitosan-GPTMS-β-GP) hybrid microspheres were synthetized through sol-gel processing using a microfluidic approach. Microspheres with uniform spherical shapes and sizes of approximately 650μm were obtained. The microstructures of the microspheres consisted of four different siloxane structures. The degradation behaviors of the hybrid microspheres were examined under acidic pH conditions mimicking those found in the gastrointestinal track. Microspheres with different GPTMS molar ratios were incubated under several pH conditions for 2weeks. The microspheres incubated at pH7.4 extended the lowest weight loss (27%-32%), whereas those incubated at pH1.7 and pH5.4 showed greater weight losses of 43-59% and 69-77%, respectively. The inhibition of the degradation at low pH was dependent on the siloxane network in the chitosan matrix. Phosphate was mostly released in early stages, and the released amount of silicon was dependent on the composition. GPTMS was released with a chitosan chain via the hydrolysis of a chitosan molecule. The pelargonidin was incorporated in the microspheres and the slow releasing was observed at acidic condition. The resistance of these hybrid microspheres to low-pH conditions for longer than a full digestion cycle is promising for gastrointestinal drug delivery applications.

摘要

壳聚糖微球作为药物递送系统时,由于其粘膜粘附性,能够解决生物利用度低或药物释放不持续等相关挑战,这使得药物剂量能够在胃肠道中长时间保留。壳聚糖-3-缩水甘油醚丙基三甲氧基硅烷-β-甘油磷酸酯(壳聚糖-GPTMS-β-GP)杂化微球通过微流控方法的溶胶-凝胶工艺合成。获得了形状均匀、尺寸约为650μm的球形微球。微球的微观结构由四种不同的硅氧烷结构组成。在模拟胃肠道中发现的酸性pH条件下研究了杂化微球的降解行为。将具有不同GPTMS摩尔比的微球在几种pH条件下孵育2周。在pH7.4下孵育的微球重量损失最低(27%-32%),而在pH1.7和pH5.4下孵育的微球重量损失分别更大,为43%-59%和69%-77%。低pH下对降解的抑制取决于壳聚糖基质中的硅氧烷网络。磷酸盐大多在早期释放,硅的释放量取决于组成。GPTMS通过壳聚糖分子的水解与壳聚糖链一起释放。天竺葵素被包封在微球中,并且在酸性条件下观察到缓慢释放。这些杂化微球在低pH条件下超过一个完整消化周期的耐受性对于胃肠道药物递送应用很有前景。

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