In vitro and in vivo amelioration of colitis using targeted delivery system of cyclosporine a in New Zealand rabbits

Abstract

Necessity to develop the efficient targeted delivery of highly potent immunosuppressant for IBD in order to avoid surgical procedure, led to fabrication and evaluation of its anti-inflammatory potential. Previously formulated cyclosporine A (Cyp A) into enteric coated capsules was further evaluated for its site-specificity in the treatment of TNBS induced colitis. Contact angle measurement studies showed excellent spreadability of the developed formulation over the hydrophilic biological tissue substrate. HET-CAM study demonstrates that the formulation prepared is nonirritant to the highly vascular tissues and hence can be used for the immunological sensitive tissues like inflamed intestine in IBD. Further the developed formulation has been characterized for site specificity to distal parts of intestine by pharmacokinetic studies. The appearance of drug in systemic circulation at approximately 5 hours in New Zealand strain of rabbits confirms drug delivery at distal parts of intestine. Significant reduced levels of TNF-α, IL-6 and IL-10 in drug treated animals signifies inhibition of inflammatory reactions at the TNBS treated site. Simultaneously, the change in body weight of same group of animals was observed for 15 days. Results showed a marginal recovery of body weight in Cyp A treated TNBS induced colitis animals. In conclusion, all in vitro and in vivo results confirm the successful site specific delivery and anti-inflammatory efficacy of developed formulation of Cyp A in TNBS induced colitis in New Zealand rabbits.