PARTICLE UPTAKE AND TRANSLOCATION ACROSS EPITHELIAL MEMBRANES

Oral delivery of drugs and vaccines has many advantages over other rou tes of administration. For example, for vaccination, enteric delivery may result in the induction of a mucosal immune response against patho gens which colonise and invade the mucosa. However, the oral delivery of peptide or protein drugs or antigens is beset with problems, such a s gastrointestinal breakdown of labile molecules, low level of macromo lecular absorption and, for vaccines, the poor immune response usually elicited by orally administered soluble antigens. Investigations are therefore in progress to develop means of increasing intestinal absorp tion and decreasing digestion of orally administered molecules. Molecu les can be incorporated into biodegradable microparticles to reduce th e effect of gut secretions and to enable the absorption of bioactive a gents in an unaltered form. The uptake of microparticulates through th e gut wall is accepted as a true biological phenomenon but the mechani sm and route of uptake have not been established. Furthermore, in gene ral, only small numbers of microparticles are translocated across epit helial membranes, possibly making these systems inappropriate for drug or vaccine delivery. This paper reviews particle uptake across the ga strointestinal tract and describes studies carried out to determine wh ether a humoral response can be elicited following oral administration of an antigen associated with biodegradable poly(DL lactide-coglycoli de) microparticles. The use of lipid delivery vehicles to enhance micr oparticle uptake and the selective transport of microspheres across M cells is also described.