Gastrointestinal transit and mucoadhesion of colloidal suspensions of Lycopersicon esculentum L. and Lotus tetragonolobus lectin-PLA microsphere conjugates in rats.

PURPOSE: To investigate in vivo the fate and the behavior of lectin-particle conjugates after oral administration. METHODS: Two plant lectins were selected, namely Lycopersicon esculentum L. and Lotus tetragonolobus lectins, which have been reported to be specific for oligomers of N-acetyl-D-glucosamine and L-fucose, respectively, and conjugated to small poly(lactide) microspheres. Their intestinal transit was investigated in detail using radiolabeled particles. The transport and the distribution of the particles along the intestine, as well as their interactions with the intestinal mucosa, were determined after oral administration in rat. RESULTS: The overall transit of the particles was shown to be strongly delayed when the microspheres were conjugated to the lectins, mainly due to the gastric retention of the particles. A significant fraction of the conjugates adhered to the gastric and intestinal mucosae. No significant differences were observed after a preliminary incubation of lectin-microsphere conjugates with specific sugars. CONCLUSION: Although specific interactions could not be excluded, especially in the stomach, it was likely that adhesion was predominantly due to nonspecific interactions. These results could be attributed both to unfavorable physicochemical characteristics of the conjugates and to premature adsorption of soluble mucin glycoproteins, preventing any further specific adhesion.

Covalent coupling of asparagus pea and tomato lectins to poly(lactide) microspheres.

Lectin-poly(lactide) microsphere conjugates specifically designed for oral administration were prepared and their activity and specificity in presence of mucus were characterized. The presence of hydroxyl or amino groups suitable for covalent coupling of lectins by the glutaraldehyde method at the surface of the microspheres have been ensured by preparing the particles in presence either of poly(vinyl alcohol) (PVA) or bovine serum albumin (BSA). Tomato and asparagus pea lectins could be covalently attached to these particles (1.0-1.3 mg/m(2) of particles). The conjugates demonstrated a 4-10 fold increase in their interactions with mucus compared to control particles. Moreover, the sugar specificity of the lectins was maintained.