期刊
JOURNAL OF CROHNS & COLITIS
卷 9, 期 8, 页码 647-658出版社
OXFORD UNIV PRESS
DOI: 10.1093/ecco-jcc/jjv089
关键词
IBD; TGF beta; ATRA
资金
- National Institutes of Health [5R44AI080009-04]
Background and aims: We investigated oral delivery of transforming growth factor beta 1 [TGF beta]- and all-trans retinoic acid [ATRA]-loaded microspheres as therapy for gut inflammation in murine models of inflammatory bowel disease [IBD]. Methods: ATRA and TGF beta were separately encapsulated in poly [lactic-co-glycolic] acid or polylactic acid microspheres [respectively]. TGF beta was encapsulated using proprietary phase-inversion nanoencapsulation [PIN (R)] technology. Results: PIN (R) 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 degrees C or -20 degrees 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 [similar to 50%], serum amyloid A levels [similar to 5-fold], colon weight-to-length ratio [similar to 50%], and histological score [similar to 5-fold]. Conclusions: Both agents given together outperformed either separately. Highest TGF beta 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.
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