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用于聚合物和聚合物包衣颗粒的新型粘膜粘附测试,以设计最佳的粘膜粘附药物递送系统。

Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems.

作者信息

Takeuchi Hirofumi, Thongborisute Jringjai, Matsui Yuji, Sugihara Hikaru, Yamamoto Hiromitsu, Kawashima Yoshiaki

机构信息

Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Japan 5-6-1 Mitahora-Higashi Gifu, 502-8585, Japan.

出版信息

Adv Drug Deliv Rev. 2005 Nov 3;57(11):1583-94. doi: 10.1016/j.addr.2005.07.008. Epub 2005 Sep 16.

Abstract

To design an effective particulate drug delivery system having mucoadhesive function, several mucoadhesion tests for polymers and the resultant particulate systems were developed. Mucin particle method is a simple mucoadhesion test for polymers, in which the commercial mucin particles are used. By measuring the change in particle size or zeta potential of the mucin particle in a certain concentration of polymer solution, we could estimate the extent of their mucoadhesive property. BIACORE method is also a novel mucoadhesion test for polymers. On passing through the mucin suspension on the polymer-immobilized chip of BIACORE instrument, the interaction was quantitatively evaluated with the change in its response diagram. By using these mucoadhesion tests, we detected a strong mucoadhesive property of several types of chitosan and Carbopol. Evaluation of mucoadhesive property of polymer-coated particulate systems was demonstrated with the particle counting method developed by us. To detect the mucoadhesive phenomena in the intestinal tract, we observed the rat intestine with the confocal laser scanning microscope (CLSM) after oral administration of the particulate systems. The resultant photographs clearly showed a longer retention of submicron-sized chitosan-coated liposomes (ssCS-Lip) in the intestinal tract than other liposomal particles tested such as non-coated liposomes and chitosan-coated multilamellar one. These observations explained well the superiority of the ssCS-Lip as drug carrier in oral administration of calcitonin in rats than other liposomal particles.

摘要

为了设计一种具有粘膜粘附功能的有效微粒药物递送系统,开发了几种针对聚合物和所得微粒系统的粘膜粘附测试方法。粘蛋白颗粒法是一种针对聚合物的简单粘膜粘附测试方法,其中使用商业粘蛋白颗粒。通过测量一定浓度聚合物溶液中粘蛋白颗粒的粒径或zeta电位变化,我们可以估计它们的粘膜粘附性能程度。BIACORE法也是一种针对聚合物的新型粘膜粘附测试方法。当通过BIACORE仪器的聚合物固定芯片上的粘蛋白悬浮液时,通过其响应图的变化对相互作用进行定量评估。通过使用这些粘膜粘附测试,我们检测到几种壳聚糖和卡波姆具有很强的粘膜粘附性能。我们开发的颗粒计数法证明了对聚合物包衣微粒系统粘膜粘附性能的评估。为了检测肠道中的粘膜粘附现象,在口服微粒系统后,我们用共聚焦激光扫描显微镜(CLSM)观察了大鼠肠道。所得照片清楚地表明,与其他测试的脂质体颗粒(如未包衣的脂质体和壳聚糖包衣的多层脂质体)相比,亚微米级壳聚糖包衣脂质体(ssCS-Lip)在肠道中的保留时间更长。这些观察结果很好地解释了ssCS-Lip作为大鼠口服降钙素药物载体比其他脂质体颗粒更具优势。

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