权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Structural Design of Micro-and Nano-gel Particles for Appropriate Controlled Release of Peptide Drugs

用于适当控制释放肽类药物的微米和纳米凝胶颗粒的结构设计

基本信息

批准号：
16590038
负责人：
ICHIKAWA Hideki
金额：
$ 2.3万
依托单位：
Kobe Gakuin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

The aim of the present research project is to develop nano-and micro-particulate systems with appropriate controlled release functions for peptide drug delivery. The proposed systems are directed to long-term delayed release for peroral colon-specific peptide delivery, externally temperature-activated periodically pulsatile release for chronopharmacological peptide delivery, and pH-dependent prolonged release using thermo-and pH-sensitive nanogels for oral peptide delivery. The results obtained are summarized as follows :1. The microcapsules composed of a lactose core, an insulin-layer and a coat of newly synthesized acrylic terpolymer made it possible to achieve a pH-independent delayed-release characterized by a lag-time and subsequent rapid insulin release. The microencapsulated insulin was found to be stable even after the storage at 4℃ for 24 months. In vivo oral administration studies of the microcapsules with a lag-time of 6h revealed a significant hypoglycemic effect, indicatin … More g insulin absorption through the colon. The pharmacological availability reached 5.1%.2. The microcapsules having an ability to thermosensitively control the drug-release could be achieved by fabricating an ethylcellulose matrix coat containing nano-sized p(NIPAAm) hydrogels onto a drug-layered core. Introduction of poly(□-caprolactone) macromer into p(NIPAAm) nanogels or use of hydroxypropylcellulose as an alternative thermosensitively component was useful to achieve distinct thermosensitive periodical pulsatile release.3. The nanogels composed of thermosensitive p(NIPAAm) core and pH sensitive (MAA-g-EG) shells (CSNPs) for oral peptide delivery were characterized in terms of drug loading capacity and muco-adhesive properties. Newly established drug-loading method was useful to significantly increase drug content (20 wt%). Atomic force microscopy (AFM) using colloidal probe of CSNPs for analyzing particle-mucin layer interaction could also be established : pH-dependent changes of interaction force were observed between CSNPs and mucin layer.4. As a solvent-free preparation process, dry-powder coating technique could be established. This technology is expected to process moisture-sensitive peptide-drug stably in an aseptic condition. Less

本研究的目的是开发具有适当控制释放功能的纳米和微米微粒系统用于肽药物递送。所提出的系统涉及用于经口结肠特异性肽递送的长期延迟释放、用于时间药理学肽递送的外部温度激活的周期性脉冲释放以及用于经口肽递送的使用热和pH敏感性纳米凝胶的pH依赖性延长释放。主要研究结果如下：1.微囊由乳糖芯、胰岛素层和新合成的丙烯酸酯涂层组成，使得能够实现以滞后时间和随后的快速胰岛素释放为特征的pH非依赖性延迟释放。微囊化胰岛素在4℃下储存24个月后仍保持稳定。体内口服给药研究表明，该微囊具有显著的降血糖作用， ...更多信息 g胰岛素通过结肠吸收。药理利用度为5.1%。具有热敏控制药物释放能力的微囊可以通过在药物层芯上制备含有纳米级p（NIPAAm）水凝胶的乙基纤维素基质包衣来实现。在p（NIPAAm）纳米凝胶中引入聚（□-己内酯）大分子单体或使用羟丙基纤维素作为替代热敏组分可用于实现明显的热敏周期性脉冲释放.制备了以p（NIPAAm）为核、pH敏感（MAA-g-EG）为壳的纳米凝胶（CSNPs），考察了其载药量和粘膜粘附性能。新建立的载药方法有助于显着提高药物含量（20 wt%）。利用CSNPs胶体探针的原子力显微镜（AFM）分析颗粒与粘蛋白层的相互作用，观察到CSNPs与粘蛋白层之间的相互作用力随pH值的变化.作为一种无溶剂制备工艺，干粉包衣技术可以建立。该技术有望在无菌条件下稳定地处理对水分敏感的肽-药物。少