Therapeutic effect of vitamin D₃-containing nanostructured lipid carriers on inflammatory bowel disease

The active form of vitamin D₃, 1,25(OH)₂D₃ has been found to exert multiple effects on the suppression of progression of inflammatory bowel disease (IBD). Vitamin D₃ has been gathering attention as a therapy for IBD. However, the clinical trials conducted to date revealed that a relatively high dosage of vitamin D₃ was required to see a significant therapeutic effect. Thus, effective formulation and delivery of vitamin D₃ to colonic inflammatory lesions will be required. Herein we describe the preparation of a nanostructured lipid carrier (NLC) for the encapsulation of 1,25(OH)₂D₃ for colonic delivery via oral administration. The optimized fabrication procedure enabled the incorporation of 1,25(OH)₂D₃ in the NLC by minimizing the destruction of chemically unstable 1,25(OH)₂D₃. The obtained NLCs orally delivered 1,25(OH)₂D₃ to the colon in mice and maintained a high concentration of 1,25(OH)₂D₃ in the colonic tissue for at least 12 h. The NLC showed multiple effects on the suppression of symptoms of colitis induced by dextran sodium sulfate, namely maintaining crypt structure, reducing the tissue concentration of inflammatory cytokines, suppressing the infiltration of polymorphonuclear leukocytes, and augmenting anti-inflammatory CX₃CR1^high macrophages. Our NLCs containing 1,25(OH)₂D₃ may be an alternative treatment for IBD therapy.