Targeting to intestinal M cells.
The specialised, antigen-transporting, epithelial M cells in the follicle-associated epithelium (FAE) overlying gut-associated lymphoid tissues constitute the primary target for oral delivery of vaccines. Our studies have shown that polystyrene microspheres selectively bind to, and are efficiently transcytosed by, rabbit Peyer's patch M cells in closed intestinal loops. Binding of biodegradable poly(DL-lactide-co-glycolide) microspheres to rabbit Peyer's patch FAE is an order of magnitude lower than that of polystyrene microspheres. Although poly(DL-lactide-co-glycolide) microspheres are not selectively targeted to M cells, a high proportion of those which bind to M cells are transcytosed, supporting the potential of such microspheres as vehicles for oral vaccine 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 depends on the surface properties of both cells and microspheres and suggest that surface modification may enhance the efficacy of microsphere delivery vehicles. One such approach is the incorporation of molecules with inherent binding specificity for M cells. Lectin-binding studies have revealed that M cells exhibit pronounced regional and species variation in glycoconjugate expression. In murine intestine, certain lectins bind selectively to M cells either in Peyer's patches or caecum, or at both sites. Selective targeting to, and transcytosis of, lectin-conjugates by M cells in ligated segments of murine intestine have also been demonstrated. While several lectins display strong selectivity for rabbit caecal M cells, none to date have been identified with specificity for rabbit or rat Peyer's patch M cells. Knowledge of human M cells is limited and no lectin has yet been identified with specificity for these cells. However, at least one lectin exhibits binding specificity for FAE in the human ileum. In the future, knowledge of the regional patterns of M cell carbohydrate expression within a species may allow lectins to be utilised to target selectively antigenic material to the mucosal immune system at specific locations.
Jepson
M A
MA
Department of Physiological Sciences, University of Newcastle upon Tyne Medical School, UK.
Clark
M A
MA
Foster
N
N
Mason
C M
CM
Bennett
M K
MK
Simmons
N L
NL
Hirst
B H
BH
D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D007408:Intestinal Absorption / Q000502:physiology*; D037102:Lectins / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D008863:Microspheres; D010581:Peyer's Patches / Q000166:cytology* / Q000502:physiology*; D011137:Polystyrenes / Q000493:pharmacokinetics; D011817:Rabbits; D051381:Rats
D037102:Lectins; D011137:Polystyrenes