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喜树碱与阳离子表面活性剂固定化后向含有阴离子卡拉胶的琼脂糖水凝胶中的扩散。

Diffusion of camptothecin immobilized with cationic surfactant into agarose hydrogel containing anionic carrageenan.

作者信息

Liu Jianhong, Li Lin

机构信息

College of Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.

出版信息

J Biomed Mater Res A. 2007 Dec 15;83(4):1103-1109. doi: 10.1002/jbm.a.31445.

Abstract

Camptothecin (CPT) is a hydrophobic antitumor drug. Controlled release of CPT from hydrogel has not been satisfactorily achieved because of its poor compatibility and weak interaction with a hydrophilic hydrogel matrix. A new approach has been attempted in this work to solve these problems. In our approach, CPT was first solubilized in a micellar solution of cetyltrimethylammonium bromide (CTAB), a cationic surfactant. It was found that the solubility of CPT could be enhanced by CTAB (10 mM) to 0.17 mg/mL, which is 127 times higher than that in pure water, providing a great feasibility of drug loading. The micellar drug solution of CTAB-CPT was subsequently used to prepare agarose hydrogels containing a small content (<or= 0.3 wt %) of kappa-carrageenan, an anionic water-soluble polysaccharide. The release of CPT from so fabricated hydrogel-surfactant systems has been investigated by varying the content of kappa-carrageenan in the hydrogel. It was observed that the presence of kappa-carrageenan in the hydrogel system resulted in a significant decrease in the release rate of the drug. This effect was ascribed to the ionic interaction between the positively charged surfactant micelles and the negatively charged kappa-carrageenan. The release profiles were fitted to two mathematic models of diffusion and the diffusion coefficients of the drug were obtained as a function of kappa-carrageenan content.

摘要

喜树碱(CPT)是一种疏水性抗肿瘤药物。由于其与亲水性水凝胶基质的相容性差且相互作用弱,尚未令人满意地实现从水凝胶中控制释放CPT。在这项工作中尝试了一种新方法来解决这些问题。在我们的方法中,CPT首先溶解在阳离子表面活性剂十六烷基三甲基溴化铵(CTAB)的胶束溶液中。发现CTAB(10 mM)可将CPT的溶解度提高到0.17 mg/mL,这比在纯水中的溶解度高127倍,为药物负载提供了很大的可行性。随后使用CTAB-CPT的胶束药物溶液来制备含有少量(≤0.3 wt%)κ-卡拉胶(一种阴离子水溶性多糖)的琼脂糖水凝胶。通过改变水凝胶中κ-卡拉胶的含量,研究了CPT从如此制备的水凝胶-表面活性剂体系中的释放情况。观察到水凝胶体系中κ-卡拉胶的存在导致药物释放速率显著降低。这种效应归因于带正电的表面活性剂胶束与带负电的κ-卡拉胶之间的离子相互作用。将释放曲线拟合到两种扩散数学模型,并获得了药物扩散系数与κ-卡拉胶含量的函数关系。

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