Biodegradable Nanoparticles for Targeted Drug Delivery in Treatment of Inflammatory Bowel Disease

TLDR

Local drug delivery via nanoparticles offers a distinct improvement over existing colon delivery devices and highlights the importance of targeting inflamed tissue in inflammatory bowel disease. The study examined targeted oral nanoparticle delivery of rolipram to inflamed gut tissue in inflammatory bowel disease. An experimental colitis model was induced in male Wistar rats, and rolipram-loaded PLGA nanoparticles were orally administered once daily for five days while clinical activity, myeloperoxidase activity, and an adverse effect index were monitored. Rolipram-loaded nanoparticles were as effective as the free drug in reducing colitis, maintained lower inflammation after drug withdrawal, and significantly reduced systemic adverse effects, demonstrating superior accumulation in inflamed tissue compared to solution.

Abstract

The use of nanoparticles for targeted oral drug delivery to the inflamed gut tissue in inflammatory bowel disease was examined. Such a strategy of local drug delivery would be a distinct improvement compared with existing colon delivery devices for this disease. An experimental colitis was induced by trinitrobenzenesulfonic acid to male Wistar rats. Rolipram, an anti-inflammatory model drug, was incorporated within poly(lactic-coglycolic acid) nanoparticles, which were administered once a day orally for five consecutive days. A clinical activity score and myeloperoxidase activity were determined to assess the inflammation, whereas an adverse effect index reflected the remaining neurotropic effect of rolipram resulting from its systemic absorption. All nanoparticle formulations proved to be as efficient as the drug in solution in mitigating the experimental colitis. The clinical activity score and myeloperoxidase activity decreased significantly after the oral administration of rolipram nanoparticles or solution. During the next 5 days when animals were kept without drug treatment the drug solution group displayed a strong relapse, whereas the nanoparticle groups continued to show reduced inflammation levels. The rolipram solution group had a high adverse effect index, whereas the rolipram nanoparticle groups proved their potential to retain the drug from systemic absorption as evidenced by a significantly reduced index. This new delivery system enabled the drug to accumulate in the inflamed tissue with higher efficiency than when given as solution. The nanoparticle deposition in the inflamed tissue should be given particular consideration in the design of new carrier systems for the treatment of inflammatory bowel disease.