Effect of Size and Loading of Retinoic Acid in Polyvinyl Butyrate Nanoparticles on Amelioration of Colitis.

Butyrate has been used in the treatment of inflammatory bowel diseases (IBD). However, the controlled release of butyrate has been indicated to be necessary in order to avoid the side effects verified at high concentrations. We previously developed nanoparticles (NPs) of polyvinyl butyrate (PVBu) as an oral butyrate donor for the controlled release of butyrate for the treatment of colitis. To examine the effect of the size of NPs on the therapeutic effect of colitis, here we prepared PVBu NPs with different sizes (100 nm and 200 nm). Both sizes of PVBu NPs significantly suppressed the inflammatory response in macrophages in vitro. PVBu NPs with 200 nm showed better effects on the amelioration of colitis compared with the 100 nm-NPs. We found unexpectedly that 200 nm-NP incorporated with all-trans retinoic acid (ATRA) showed a much better therapeutic effect than those with unloaded 200 nm-NPs, although ATRA alone was reported to worsen the inflammation. The synergistic effect of ATRA with butyrate shows evidence of being a promising approach for IBD treatment.