TARGETING TO INTESTINAL M-CELL

The specialised, antigen-transporting, epithelial M cells in the folli cle-associated epithelium (FAE) overlying gut-associated lymphoid tiss ues constitute the primary target for oral delivery of vaccines. Our s tudies have shown that polystyrene microspheres selectively bind to, a nd are efficiently transcytosed by, rabbit Peyer's patch M cellsin clo sed intestinal loops. Binding of biodegradable poly(DL-lactide-co-glyc olide) microspheres to rabbit Peyer's patch FAE is an order of magnitu de lower than that of polystyrene microspheres. Although poly(DL-lacti de-co-glycolide) microspheres are not selectively targeted to M cells, a high proportion of those which bind to M cells are transcytosed, su pporting the potential of such microspheres as vehicles for oral vacci ne delivery. Comparison of the binding of polystyrene microspheres by murine FAE revealed this to be markedly less extensive than by rabbit FAE. These data demonstrate that microsphere binding by M cells depend s on the surface properties of both cells and microspheres and suggest that surface modification may enhance the efficacy of microsphere del ivery vehicles. One such approach is the incorporation of molecules wi th inherent binding specificity for M cells. Lectin-binding studies ha ve revealed that M cells exhibit pronounced regional and species varia tion in glycoconjugate expression. In murine intestine, certain lectin s bind selectively to M cells either in Peyer's patches or caecum, or al both sites. Selective targeting to, and transcytosis of, lectin-con jugates by M cells in ligated segments of murine intestine have also b een demonstrated. While several lectins display strong selectivity for rabbit caecal M cells, none to date have been identified with specifi city for rabbit or rat Peyer's patch M cells. Knowledge of human M cel ls is limited and no lectin has yet been identified with specificity f or these cells. However, at least one lectin exhibits binding specific ity for FAE in the human ileum. In the future, knowledge of the region al patterns of M cell carbohydrate expression within a species may all ow lectins to be utilised to target selectively antigenic material to the mucosal immune system at specific locations.