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Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease

August 30, 2017

3:30 PM - 4:30 PM

Presented by: Dulari Jayawardena, PhD Candidate
Advisor: Dr. Hayat Onyuksel
Department of Biopharmaceutical Sciences, UIC
UIC College of Pharmacy
833 S. Wood Street
Room 134-3/ E223 Rockford
Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a wide array of immunomodulatory properties. VIP has shown beneficial effects in managing multiple inflammatory disorders, including inflammatory bowel disease (IBD). IBD includes chronic disorders of the gastro intestinal tract, namely Crohn’s disease (CD) ­and ulcerative colitis (UC). The usage of VIP is hindered by its short biological half-life and off target effects (hypotension). To overcome these delivery challenges, we have developed a biocompatible nanoparticle (VIP-SSM), which can successfully deliver active VIP to the target tissue to treat IBD. The studies herein were designed to determine the therapeutic benefit of intra peritoneally (ip) administered VIP-SSM in managing IBD, utilizing mouse models of colitis resembling both CD (trinitrobenzene sulfonic acid/TNBS induced colitis) and UC (dextran sulfate sodium/DSS induced colitis). Since IBD is an intestinal disease, delivering VIP-SSM via oral route would be more beneficial. To this end, we have tested the effectiveness of administering the nanoparticle intra luminally to the colon. Finally, we hope to test the prospects of scaling up the nanomedicine for clinical use via oral formulation by incorporating the nanomedicine to enteric-coated capsules. Our results demonstrate that ip administered VIP-SSM is effective in alleviating inflammation associated with both DSS and TNBS colitis. VIP-SSM significantly reduced the inflammation and associated diarrhea in colitis by affecting pro-inflammatory cytokine mRNA expression, histology, tight junction proteins, secreted mucus and ion transporter expression in the distal colon. These beneficial effects were also apparent when the nanomedicine was administered intra rectally to the colonic lumen, showing potential for oral delivery. Together, our data indicate the effectiveness of VIP-SSM as a therapeutic agent in managing IBD, and shows proof of concept of its use as a novel oral product.


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