A comparative study of curcumin-loaded lipid-based nanocarriers in the treatment of inflammatory bowel disease

•Three lipid nanocarriers containing curcumin (CC) were evaluated for IBD treatment.•Nanocapsules (NC) exhibited a 30-fold higher CC permeability across Caco-2 cells.•CC SNEDDS and CC NLC but not CC NC significantly reduced TNF-α secretion in vitro.•In vivo, only CC NLC were able to significantly decrease MPO and TNF-α secretion.•Higher CC permeability did not correlate with a higher efficacy in IBD treatment.

Selective drug delivery to inflamed tissues is of widespread interest for the treatment of inflammatory bowel disease (IBD). Because a lack of physiological lipids has been described in patients suffering IBD, and some lipids present immunomodulatory properties, we hypothesize that the combination of lipids and anti-inflammatory drugs together within a nanocarrier may be a valuable strategy for overcoming IBD. In the present study, we investigated and compared the in vitro and in vivo efficacy of three lipid-based nanocarriers containing curcumin (CC) as an anti-inflammatory drug for treating IBD in a murine DSS-induced colitis model. These nanocarriers included self-nanoemulsifying drug delivery systems (SNEDDS), nanostructured lipid carriers (NLC) and lipid core-shell protamine nanocapsules (NC). In vitro, a 30-fold higher CC permeability across Caco-2 cell monolayers was obtained using NC compared to SNEDDS (NC > SNEDDS > NLC and CC suspension). The CC SNEDDS and CC NLC but not the CC NC or CC suspension significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, only CC NLC were able to significantly decrease neutrophil infiltration and TNF-α secretion and, thus, colonic inflammation. Our results show that a higher CC permeability does not correlate with a higher efficacy in IBD treatment, which suggests that lipidic nanocarriers exhibiting increased CC retention at the intestinal site, rather than increased CC permeability are efficient treatments of IBD.

Graphical abstractA schematic overview of the efficiency of CC-loaded lipid-based nanocarriers in treating IBD.Figure optionsDownload full-size imageDownload as PowerPoint slide