Probing the particle shape effects on the biodistribution and antihyperlipidemic efficiency for oral lovastatin nanocrystals

Abstract

For nanocrystals (NCs), particle shapes were proven to be a significant factor affecting the transport behaviors across the intestinal barriers. However, the effects of particle shapes on oral biodistribution and pharmacodynamics remain unclear. In the present study, lovastatin (LOV) was selected as a model drug, and we prepared spherical, rod-shaped and flaky like LOV NCs to investigate how particle shapes influence the intestinal absorption, in vivo fate and lipid-lowering effects. First, Caco-2/HT-29 MTX co-cultured cell model was established to mimic intestinal epithelial and to investigate the absorption and transcellular transport ability. Then, in situ intestinal absorption with/without peyer's patches were studied. The results showed that LOV NCs were mainly uptake by enterocytes, while M-cells could only contribute to limited absorption. The ex vivo study of oral biodistribution results exhibited that RNCs showed longer retention time in the gastrointestinal tract and more accumulation in liver. Finally, the pharmacodynamics study was conducted in hyperlipidemia rats. The results revealed that RNCs were superior in reducing blood lipid levels, reducing liver index, reversing liver injuries and decreasing serum inflammatory factors levels. Besides, no muscle damage was observed at a dosage of 10 mg/kg LOV every day. In summary, particle shapes were essential parameters for developing NCs, and RNCs were promising to be optimal NCs for LOV with superior lipid-lowering effects and minimum side effects.