Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the peyer's patches

Abstract

Microspheres prepared from various polymers were evaluated for their usefulness as carriers for the targeted delivery of vaccine antigens to the gut-associated lymphoid tissues. Following oral administration to mice, microspheres consisting of polystyrene, poly(methyl methacrylate), poly(hydroxybutyrate), poly( dl-lactide), poly( l-lactide), and of poly( dl-lactide-co-glycolide) with various ratios of lactide to glycolide were absorbed into the Peyer's patches of the small intestine. In contrast, no or very little uptake was observed with microspheres consisting of ethyl cellulose, cellulose acetate hydrogen phthalate or cellulose triacetate. Tissue penetration was specific to the Peyer's patches and was restricted to microspheres ⩽ 10 μm in diameter. Time-course studies on the fate of the poly( dl-lactide-co-glycolide) microspheres within the gut-associated lymphoid tissue showed that the majority of the microspheres < 5 μm in diameter were transported through the efferent lymphatics within macrophages, while the majority of those 5 μm in diameter remained fixed in the Peyer's patches. Poly ( dl-lactide-co-glycolide) microspheres containing a toxoid vaccine of staphylococcal enterotoxin B were prepared and characterized for their size distribution, surface morphology and toxoid release kinetics in an aqueous environment. Oral immunization with these microspheres effectively delivered and released the vaccine in the gutassociated lymphoid tissue as determined by their ability to induce a disseminated mucosal IgA anti-toxin antibody response.