Journal
JOURNAL OF CONTROLLED RELEASE
Volume 286, Issue -, Pages 94-102Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.07.019
Keywords
Inflammatory bowel disease; Vitamin D-3; Oral administration; Inflammatory disease; Nanostructured lipid carrier
Funding
- Kobayashi International Scholarship Foundation
- MEXT scholarship
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The active form of vitamin D-3, 1,25(OH)(2)D-3 has been found to exert multiple effects on the suppression of progression of inflammatory bowel disease (IBD). Vitamin D-3 has been gathering attention as a therapy for IBD. However, the clinical trials conducted to date revealed that a relatively high dosage of vitamin D-3 was required to see a significant therapeutic effect. Thus, effective formulation and delivery of vitamin D-3 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)(2)D-3 for colonic delivery via oral administration. The optimized fabrication procedure enabled the incorporation of 1,25(OH)(2)D-3 in the NLC by minimizing the destruction of chemically unstable 1,25(OH)(2)D-3. The obtained NLCs orally delivered 1,25(OH)(2)D-3 to the colon in mice and maintained a high concentration of 1,25(OH)(2)D-3 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 CX3CR1high macrophages. Our NLCs containing 1,25(OH)(2)D-3 may be an alternative treatment for IBD therapy.
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