The potential use of tomato lectin for oral drug delivery: 3. Bioadhesion in vivo

Abstract

125I-labelled tomato lectin ([ 125I]TL) was evaluated as a bioadhesive for oral drug delivery following intra-gastric administration to adult rats. It was compared with two control molecules, [ 125I]polyvinylpyrrolidone ([ 125I]PVP), an inert polymer, and 125I-labelled bovine serum albumin ([ 125I]BSA), a degradable protein of similar molecular weight. The intestinal transit, body distribution and degradation of the macromolecules were determined 1, 5, 10 or 24 h after oral feeding and the behaviour and patterns of distribution were compared. TL was found to be resistant to degradation, with 12% of the recovered dose appearing as high molecular weight fractions in the faeces after 24 h. After 1 and 5 h, 80 and 50% of the recovered activity was found in the gastrointestinal (GI) tract, respectively. Up to 20% of the radioactivity was associated with intestinal tissue at these time points. 100% of the PVP was recovered in the faeces after 24 h. At 1 and 5 h, virtually all the PVP activity was associated with intestinal washings. BSA was degraded completely during transit with 95% of the recovered activity found in the urine and 5% in the thyroid gland after 24 h. Although these results indicate that TL is resistant to degradation in the GI tract and that it adheres to intestinal tissue, little difference was seen in the transit times of TL and PVP. This may have been due to interactions of TL with intestinal mucus and could limit the potential of TL for use as an intestinal bioadhesive.