Nanoparticles enhance therapeutic efficiency by selectively increased local drug dose in experimental colitis in rats.

Nanoparticles (NP) are proposed for targeted drug delivery to the inflammation site in severe cases of inflammatory bowel disease where state-of-the-art delivery devices fail. FK506 (tacrolimus) entrapped into NP was administered either orally or rectally to male Wistar rats suffering from a preexisting experimental colitis. Clinical activity score, colon/body weight index, and myeloperoxidase activity were determined to assess the inflammation. Tissue penetration experiments elucidated the processes involved in the proposed new therapeutic approach. The therapeutic effects of FK506 solutions as well as FK506-NP by oral route were minor. The myeloperoxidase activity and colon/body weight ratio decreased significantly (P < 0.05) only after the rectal administration of FK506-NP, whereas treatment by free drug was not different from colitis control in both 2,4,6-trinitrobenzenesulfonic acid and oxazolone colitis model. NP allows an enhanced and selective drug penetration into the inflammation site as opposed to surrounding healthy tissue (healthy: FK506, 109 +/- 18 nmol/cm2; FK506-NP, 51 +/- 13 nmol/cm2; colitis: FK506, 79 +/- 28 nmol/cm2; FK506-NP, 105 +/- 24 nmol/cm2), presumably by protecting the encapsulated drug against influences from efflux systems and mucosal metabolism. The relative drug penetration into the inflamed tissue is about 3-fold higher compared with healthy tissue when using NP as drug carriers. The use of drug-loaded NP offers several advantages compared with standard therapeutic strategies such as a higher selectivity in adhesion to and enhanced drug penetration into the inflamed tissue.