Nanocrystals, due to high drug loading efficiency, have drawn large attention as nanotechnology to enhance solubility and bioavailability of poorly soluble drugs. However, most nanocrystals still encountered low oral absorption percentage due to its insufficient retention time in the gastrointestinal tract (GI). In this work, silybin (SB) as model drug was fabricated to nanocrystals, and further loaded into a mucoadhesive microsphere to increase the GI retention. Such mucoadhesive microspheres were prepared with a wet media milling technique followed by coagulation and film coating. Nanocrystals and microspheres were thoroughly characterized by diverse complementary techniques. As results, such delivery system displayed an encapsulation efficiency of approximately 100% and a drug loading capacity of up to 35.41 ± 0.31%. In addition, mucoadhesiveness test ex vivo conducted with rat intestine showed that film-coated microspheres were retained for more than 1 h. Benefiting from nanocrystals technology, the drug cumulative release percentage of the microspheres was remarkable improved compared to unprocessed one in vitro. Finally, pharmacokinetics studies in rats showed a significant 3-fold increase of drug oral bioavailability compared to unprocessed SB. The current study demonstrates that the developed delivery vehicle can enhance the bioavailability of SB by increasing its dissolution percentage as well as through extending retention time in the GI tract, and achieve high drug loading capacity.

由于高的药物加载效率，纳米晶体作为增强难溶性药物的溶解度和生物利用度的纳米技术已经引起了广泛的关注。然而，由于其在胃肠道（GI）中的保留时间不足，大多数纳米晶体仍然遇到低的口服吸收率。在这项工作中，水飞蓟宾（SB）作为模型药物被制备成纳米晶体，并进一步加载到粘膜粘附微球中以增加GI保留。用湿介质研磨技术制备此类粘膜粘附性微球，然后进行凝聚和膜包衣。纳米晶体和微球通过多种互补技术得到了彻底的表征。结果，这种递送系统显示出约100％的包封效率和高达35.41±0.31％的载药量。此外，用大鼠肠道进行的离体研究表明，薄膜包被的微球保留了1小时以上。得益于纳米晶体技术，与未经处理的一种体外相比，微球的药物累积释放百分比有了显着提高。最后，在大鼠体内的药代动力学研究表明，与未处理的SB相比，药物口服生物利用度显着提高了3倍。当前的研究表明，开发的递送载体可通过增加其溶出率以及延长其在胃肠道中的保留时间来提高SB的生​​物利用度，并实现高载药量。