Liu Jianhong, Li Lin
College of Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.
J Biomed Mater Res A. 2007 Dec 15;83(4):1103-1109. doi: 10.1002/jbm.a.31445.
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.
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。