GASTROINTESTINAL UPTAKE OF BIODEGRADABLE MICROPARTICLES - EFFECT OF PARTICLE-SIZE

Purpose. To investigate the effect of microparticle size on gastrointe stinal tissue uptake. Methods. Biodegradable microparticles of various sizes using polylactic polyglycolic acid (50:50) co-polymer (100 nm, 500 nm, 1 mu m, and 10 mu m) and bovine serum albumin as a model prote in were formulated by water-in-oil-in-water emulsion solvent evaporati on technique. The uptake of microparticles was studied in rat in situ intestinal loop model and quantitatively analyzed for efficiency of up take. Results. In general, the efficiency of uptake of 100 nm size par ticles by the intestinal tissue was 15-250 fold higher compared to lar ger size microparticles. The efficiency of uptake was dependent on the type of tissue, such as Peyer's patch and non patch as well as on the location of the tissue collected i.e, duodenum or ileum. Depending on the size of microparticles, the Peyer's patch tissue had 2-200 fold h igher uptake of particles than the non-patch tissue collected from the same region of the intestine. Histological evaluation of the tissue s ections demonstrated that 100 nm particles were diffused throughout th e submucosal layers while the larger size nano/microparticles were pre dominantly localized in the epithelial lining of the tissue. Conclusio ns. There is a microparticle size dependent exclusion phenomena in the gastrointestinal mucosal tissue with 100 nm size particles showing si gnificantly greater tissue uptake. This has important implications in designing of nanoparticle-based oral drug delivery systems, such as an oral vaccine system.