Biodegradable 14C-poly(D,L-lactic acid) (PLA50) nanoparticles coated either with a readily digestible protein albumin or with a non-digestible coating agent, polyvinyl alcohol (PVA), were prepared by the solvent evaporation technique. The nanoparticles were administered perorally to guinea pigs to evaluate the gastro-intestinal degradation of their PLA50 matrix. In the case of PLA50 nanoparticles coated with digestible albumin, substantial gastro-intestinal degradation of the PLA50 matrix occurred, leading to the passage of considerable amount (> or =45%) of water-soluble products across the gastrointestinal barrier. When a non-digestible coating agent like PVA was used, the degradation of the PLA50 matrix in the gastro-intestinal tract was at least two times lower (> or =19%). The results show that it is possible to control the in vivo degradation of PLA50 nanoparticles using appropriate coating agents. The present investigations showed a good correlation between previously observed in vitro results and the in vivo findings.