PLGA encapsulated polyphenols to ameliorate IBD.

Abstract Green tea has received increased attention recentlydue to several epidemiological and clinical studies showing a positive relationship between consumption and disease preventionBenefits include reduced risk of cardiovascular diseasese gmyocardial infarctionhypertensionatherosclerosisneurodegenerative diseasese gParkinson s and Alzheimer s diseaseand certain cancerse ggastricbreast and cervical cancerSupplements can even help maintain healthy body weight and lipid profilesClinical activity has been demonstrated in leukemia and by our group in inflammatory bowel diseaseIBDThese effects are attributed to the polyphenolic flavonoid compounds known as catechinsi epolyphenolspresent in high amountsYetpoor stabilitylow oral bioavailability and inconsistent intestinal absorption remain problematicIf these shortcomings were overcomethe impact of green tea supplementation could be dramatically improved and novelefficacious pharmaceutical products aimed at maintaining health developedThe hypothesis behind this application is that encapsulation into poly D L lactide co glycolidePLGAmicrospheres will improve the delivery and thus efficacy of green tea s polyphenols via the oral routeImportantlyPLGA is already approved by the FDA and EMA for human useThusPLGA based micro particles are in a good position for use in products intended for human consumptionConsidering these observationsthe proposed studies will test an oral PLGA encapsulated polyphenol formulation for prophylactic useIn Aimwe will determine whether oral administration of polyphenol loaded microspheres is superior to parenteral soluble material in limiting murine IBD using a prophylactic iteration of the acute DSS induced colitis modelWe will then optimize the prophylactic protocol and examine the effects of treatment on the phenotypic and functional properties of colonic LP and MLN mononuclear cellsIn Aimwe will determine whether oral administration of polyphenol microspheres is similarly effective in the CDCDT cell reconstituted SCID mouse model of colitis This model is also in routine operation in our laboratoryWe will elucidate immunological mechanismsas well as monitor long term efficacy and systemic side effectsFuture work will include pharmacokineticdose ranging toxicology studiesas well as product developmentdrug product and drug substanceefforts aimed at novel pharmaceutical productsIf the proposed studies are successful the hope is that the benefits of green tealong recognized by the ancientsmay at last be translated and optimized into prophylactic benefit for IBD patients NARRATIVE PUBLIC HEALH RELEVANCE This application proposes to test a novel oral formulation of green tea extract as prophylactic treatment for inflammatory bowel diseaseIBDThe hope is that the established clinical benefit of green tea may be optimized and translated into benefit for IBD patients in the form of novelprophylactic products