College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China.
School of Clinical Medicine, Weifang Medical University, Weifang, 261053, China.
Colloids Surf B Biointerfaces. 2021 Feb;198:111461. doi: 10.1016/j.colsurfb.2020.111461. Epub 2020 Nov 12.
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.
纳米晶体由于具有较高的药物负载效率，作为纳米技术被广泛关注，以提高难溶性药物的溶解度和生物利用度。然而，由于其在胃肠道（GI）中的停留时间不足，大多数纳米晶体的口服吸收率仍然较低。在这项工作中，以水飞蓟宾（SB）为模型药物制备纳米晶体，并进一步负载到粘膜粘附微球中以增加 GI 保留时间。采用湿介质研磨技术，然后进行凝聚和涂膜制备这种粘膜粘附微球。通过多种互补技术对纳米晶体和微球进行了彻底的表征。结果表明，该递药系统的包封效率约为 100%，载药量高达 35.41±0.31%。此外，用大鼠肠进行的体外粘膜粘附性试验表明，涂膜微球的滞留时间超过 1 小时。受益于纳米晶体技术，与未加工的 SB 相比，微球的药物累积释放百分比在体外得到了显著提高。最后，在大鼠中的药代动力学研究表明，与未加工的 SB 相比，药物口服生物利用度显著提高了 3 倍。本研究表明，所开发的给药载体可以通过提高药物的溶解百分比以及延长在胃肠道中的停留时间来提高 SB 的生物利用度，并实现高载药量。
