Effect of food supplement constituents Quercetin, Silibinin and Luteolin on oral uptake of protease inhibitor saquinavir: synthetic meets natural

Abstract

Saquinavir is the BCS class IV drug, it is a first protease inhibitor for HIV infection treatment, having poor permeability. The main purpose of this study was to study the effect of natural compounds on its bioavailability. In this work, binary systems of SQU with the natural bioenhancers were prepared using physical mixing method. The effect of these compounds were studied using different sophisticated experimental protocols. Firstly the compatability was tested for the three used bioenhancers quercetin (QU), silibinin (Sil), Luteolin (LT). Oral uptake was studied by analyzing the transport of SQU across the human colorectal adenocarcinoma cell line (Caco-2) cell lines. Permeation through the goat intestine tissue was also studied. Pharmacokinetic analysis was also performed in rabbits by administered SQU with different bioenhancers in the form of suspension, and the whole analytical studies for the estimation of SQU in different studies were conducted using LC-MS. In the compatibility studies, bioenhancers found to be showing no or minimal interaction with the SQU. Permeation in the intestinal tissue of goat was significantly increased as compared to the plain drug. The transport of SQU across the Caco-2 cell lines also found to be improved than the plain drug. Pharmacokinetic study showed there was increase in the Cmax by approx. 3 folds using the different bioenhancers. AUC was also found to be increase by more than 2 folds with the each bioenahncer. The maximum oral uptake enhancement was found with the QU following by the Sil and then LT.