Mucoadhesive nanocrystal-in-microspheres with high drug loading capacity for bioavailability enhancement of silybin

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.