Dreamz College of Pharmacy, Khilra-Meramesit, Sundernagar, Mandi, Himachal Pradesh, India 175036.
Mol Pharm. 2012 Nov 5;9(11):2986-94. doi: 10.1021/mp300289y. Epub 2012 Oct 16.
The aim of this study was to develop novel colon targeted mucoadhesive microspheres (MAMs) for site specific delivery of 5-fluorouracil (5-FU) to colon without the drug being released in the stomach or small intestine. MAMs were prepared using Assam Bora rice starch, a natural mucoadhesive polymer, by a double emulsion solvent evaporation method. The microspheres were characterized for their shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro and in vivo drug release studies. The release study confirmed the insignificant release of 5-FU in physiological condition of stomach and small intestine and major drug release in the cecal content. In vivo release study of the optimized MAMs was compared with immediate release (IR) 5-FU. 5-FU was distributed predominantly in the upper GI tract from the IR, whereas 5-FU was distributed primarily to the lower part of the GI tract from the MAM formulation. Enhanced levels of liver enzymes were found in animals given IR 5-FU as well as augmented levels of serum albumin, creatinine, leucocytopenia and thrombocytopenia was also observed. Thus to sum up, it can be appropriately established that the 5-FU release pattern from MAMs exhibits slow and extended release over longer periods of time with reduced systemic side effects.
本研究旨在开发新型结肠靶向型黏附微球（MAMs），用于将 5-氟尿嘧啶（5-FU）递送到结肠，而不在胃或小肠中释放药物。MAMs 是通过双重乳液溶剂蒸发法使用 Assam Bora 大米淀粉（一种天然黏附聚合物）制备的。对微球的形状、大小、表面形态、粒径分布、包封效率以及体外和体内药物释放研究进行了表征。释放研究证实，5-FU 在胃和小肠的生理条件下几乎不释放，而在盲肠内容物中则主要释放药物。将优化的 MAMs 的体内释放研究与即时释放（IR）5-FU 进行了比较。IR 5-FU 主要分布在上胃肠道，而 MAM 制剂则主要分布在胃肠道的下部。给予 IR 5-FU 的动物的肝酶水平升高，同时还观察到血清白蛋白、肌酐、白细胞减少症和血小板减少症的水平升高。因此，可以合理地认为，MAMs 中 5-FU 的释放模式表现出缓慢和延长的释放，在更长的时间内释放，同时减少全身副作用。
