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.

Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease

NICOLETTI, FERDINANDO;MANGANO, KATIA DOMENICA;
2015-01-01

Abstract

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.
File in questo prodotto:
File Dimensione Formato  
Oral delivery TGFbeta.pdf

accesso aperto

Dimensione 1.27 MB
Formato Adobe PDF
1.27 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/44508
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 18
social impact