Gastrointestinal uptake of biodegradable microparticles: effect of particle size.

Purpose. To investigate the effect of microparticle size on gastrointestinal tissue uptake. Methods. Biodegradable microparticles of various sizes using polylactic polyglycolic acid (50:50) co-polymer (100 nm, 500 nm, 1µm, and 10 µm) and bovine serum albumin as a model protein were formulated by water-in-oil-in-water emulsion solvent evaporation technique. The uptake of microparticles was studied in rat in situ intestinal loop model and quantitatively analyzed for efficiency of uptake. Results. In general, the efficiency of uptake of 100 nm size particles by the intestinal tissue was 15–250 fold higher compared to larger 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 higher uptake of particles than the non-patch tissue collected from the same region of the intestine. Histological evaluation of the tissue sections demonstrated that 100 nm particles were diffused throughout the submucosal layers while the larger size nano/microparticles were predominantly localized in the epithelial lining of the tissue. Conclusions. There is a microparticle size dependent exclusion phenomena in the gastrointestinal mucosal tissue with 100 nm size particles showing significantly greater tissue uptake. This has important implications in designing of nanoparticle-based oral drug delivery systems, such as an oral vaccine system.