Body distribution of poly-DL-lactide-poly(ethylene glycol) microspheres with entrapped Leptospira interrogans antigens following intravenous and oraladministration to guinea-pigs

Poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres with entrapped an tigens were administered intravenously and orally into guinea-pigs to quant itatively determine the in-vivo distribution and release profiles. PELA microspheres containing I-125-labelled outer-membrane protein Leptospi ra interrogans antigens (I-125-OMP) were prepared by double-emulsion solven t extraction procedure, and characterized with respect to size, morphology and in-vitro release profiles. The fractured sections of liver and spleen w ere inspected by scanning electron microscopy, which indicated that microsp heres had successfully been entrapped within the above tissues after intrav enous injection and oral administration. At predetermined intervals, the bl ood and such tissues as the liver, spleen, kidney, thyroid, small intestine and mesentery were collected, and the radioactivity was measured by gamma scintillation counting. Following intravenous administration, 56.7% of admi nistered microspheres were accumulated in immunization-related tissues, and 40.1% of microspheres were located in the liver and spleen. However, there was limited uptake efficiency (8.33%) following oral administration, and 4 9.5% of the absorbed microspheres were located in the intestinal mucosa. Co mpared with in-vitro release, the in-vivo release profiles of I-125-OMP fro m PELA microspheres, determined from the decreasing radioactivity in the ab ove tissues, were much faster and the burst effect was higher. Antigen-loaded PELA microspheres were efficiently entrapped within immuniza tion-related tissues after intravenous administration, but orally administe red PELA microspheres showed limited uptake efficiency. Further investigati on is needed to improve intestinal absorption.