Mucoadhesion of colloidal particulate systems in the gastro-intestinal tract

The oral route is the preferred route for drug delivery. However, numerous drugs remain poorly available when administered by this route. In order to circumvent this problem, it has been proposed, successfully for several of them, to associate drugs with colloidal polymeric particle systems. Orally administered nano- and microparticles can follow at least three different pathways: (i) capture by gut-associated lymphoid tissue; (ii) mucoadhesion; and (iii) direct faecal elimination. The relative importance of these different mechanisms is discussed. Emphasis has been laid on mucoadhesion which has been assessed in vitro and in vivo by using polystyrene and poly(lactic acid) nanoparticles as models. On the one hand, in vitro adsorption and desorption studies have shown that particles could be captured to a considerable extent by the mucous gel layer lining the gastro-intestinal tract through a mucoadhesion mechanism. On the other hand, the in vivo behaviour of the particles in the intestinal lumen has been accurately investigated by means of radiolabelled particles. Direct particle translocation through the intestinal mucosa was not predominant. On the contrary, a significant fraction of the particles was captured by the mucous gel layer while the remainder of the particles underwent unmodified transit. It can be concluded that the therapeutic potential of colloidal drug carriers after oral administration is probably not to deliver the drug directly into the blood flow but to increase bioavailability by protecting the drug from denaturation in the gastro-intestinal lumen, or by increasing the drug concentration for a prolonged period of time directly at the surface of the mucous membrane.