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- Title
Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease.
- Authors
Conway, Thomas F.; Hammer, Laura; Furtado, Stacia; Mathiowitz, Edith; Nicoletti, Ferdinando; Mangano, Katia; Egilmez, Nejat K.; Auci, Dominick L.
- Abstract
Background and aims: We investigated oral delivery of transforming growth factor beta 1 [TGFβ]- and all-trans retinoic acid [ATRA]-loaded microspheres as therapy for gut inflammation in murine models of inflammatory bowel disease [IBD]. Methods: ATRA and TGFβ were separately encapsulated in poly [lactic-co-glycolic] acid or polylactic acid microspheres [respectively]. TGFβ was encapsulated using proprietary phase-inversion nanoencapsulation [PIN®] technology. Results: PIN® particles provided sustained release of bioactive protein for at least 4 days and were stable for up to 52 weeks when stored at either 4°C or -20° C. In the SCID mouse CD4 + CD25- T cell transfer model of IBD, oral treatment starting at disease onset prevented weight loss, significantly reduced average disease score [~ 50%], serum amyloid A levels [~ 5-fold], colon weight-to-length ratio [~ 50%], and histological score [~ 5-fold]. Conclusions: Both agents given together outperformed either separately. Highest TGFβ doses and most frequent dose schedule were most effective. Activity was associated with a significant increase [45%] in Foxp3 expression by colonic lamina propria CD4+ CD25+ T-cells. Activity was also demonstrated in dextran sulphate sodium-induced colitis. The data support development of the combination product as a novel, targeted immune based therapy for treatment for IBD.
- Publication
Journal of Crohn's & Colitis, 2015, Vol 9, Issue 8, p647
- ISSN
1873-9946
- Publication type
Article
- DOI
10.1093/ecco-jcc/jjv089