BINDING AND UPTAKE OF BIODEGRADABLE POLY-DL-LACTIDE MICRO-PARTICLE AND NANOPARTICLE IN INTESTINAL EPITHELIA

The use of biodegradable particles as oral delivery vehicles for macro molecular drugs was investigated. We evaluated the binding. uptake and absorption of poly-DL-lactide (PLA) micro- and nanoparticles in Caco- 2 monolayers and in ileal tissue and gut associated lymphoid tissue (G ALT) of anaesthetised rats and rabbits. Using a range of experimental techniques, we found that approximately 10% of administered micro- and nanoparticles were adsorbed to the apical membranes of each of the fi ve intestinal models. Nanoparticles were found to be absorbed better t han microparticles. Overall, little discrimination in uptake patterns was evident between Peyer's parch (PP) and non-PP tissue while rat ile um showed a greater uptake capacity than rabbit. Our results show that uptake of PLA particles was low capacity, size-dependent and predomin antly transcellular in all systems. A low proportion of the apically-b ound particles was absorbed, with uptake exclusion evident for particl es >4 mu m. The affinity of PLA particles for intestinal epithelia and GALT needs to be greatly enhanced in order to achieve improved oral b ioavailability of macromolecules. (C) 1998 Elsevier Science B.V.