The potential use of tomato lectin for oral drug delivery: 2. Mechanism of uptake in vitro

Abstract

Tomato lectin (TL) is a non-toxic dietary glycoprotein of molecular mass 71 kDa. Its interaction with, and uptake by, the adult rat small intestine was investigated using an improved everted gut sac system, to evaluate its potential in oral drug delivery systems. Uptake of [ 125I]TL was compared with two control molecules; 125I-labelled polyvinylpyrrolidone (PVP), an inert polymer often used as a marker for fluid-phase endocytosis, and 125I-labelled bovine serum albumin (BSA), a degradable protein of similar molecular mass to TL. Uptake of substrate associated with gut tissue or in the serosal space was calculated as ng per mg of gut sac protein. The rate of uptake of tomato lectin into gut sac tissue at 37°C was 27 ng/h per mg protein, but passage into the serosal space was much slower (1.7 ng/h per mg protein). The rate of uptake by the tissue was 11-times higher than BSA and 20-times higher than PVP, but transfer into the serosal space was only 4.3- and 5-times greater than BSA and PVP, respectively. This showed that the proportion of lectin transferred across the mucosa to the serosa was less than either control, and indicated accumulation of TL within the enterocytes. Incubation at 4°C and with metabolic inhibitors demonstrated that the mechanism of TL uptake by small intestinal gut sacs in culture was adsorptive endocytosis. Trichloroacetic acid solubility studies showed that TL was more resistant to enzyme degradation during incubation with gut sacs than BSA. The fact that TL was shown to adhere to the gut surface, showed increased uptake when compared with control macromolecules, PVP and BSA, and accumulated in the mucosal cells, may give it potential as a drug carrier for delivery to the gastrointestinal tract.