Development, optimization and evaluation of long chain nanolipid carrier for hepatic delivery of silymarin through lymphatic transport pathway

Abstract

In the present study, nanostructured lipid carriers (NLCs) with three different lipid combinations (solid lipid:liquid lipid) were prepared through emulsification and ultrasonication using a Box–Behnken design. From the design, the best lipid combination was glyceryl monostearate and oleic acid, which gives particle of smaller size (223.73±43.39nm) with high drug entrapment efficiency (78.65±2.2%). In vitro release studies show that 84.60±5.66% of drug was released in 24h. In vivo studies revealed that drug absorption occurs through lymphatic pathway as only 5.008±0.011μg/ml of peak plasma concentration was achieved in blood plasma in presence of chylomicron inhibitor. The peak plasma concentration (Cmax) for silymarin loaded NLC was found to be 25.565±0.969μg/ml as compared to silymarin suspension whose Cmax was found to be 14.050±0.552μg/ml, this confirms 2-fold increase in relative bioavailability. In vivo studies revealed that 19.268±1.29μg of drug reaches to liver in 2h whereas negligible drug concentration reported in other organs. It was concluded that drug loaded NLCs was beneficial for targeting liver or other lymphatic disorders through lymphatic transport pathway. Finally, the main purpose of modifying lymphatic transport system was successfully achieved through NLCs.