Codelivery of 1α,25-Dihydroxyvitamin D<sub>3</sub> and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction.
Su. Yajuan Y; Ganguli-Indra. Gitali G; Bhattacharya. Nilika N; Logan. Isabelle E IE; Indra. Arup K AK; Gombart. Adrian F AF; Wong. Shannon L SL; Xie. Jingwei J
Key Findings
- Vitamin D3 and the CYP24A1 inhibitor VID400 can be co‑loaded into nanofiber dressings with >90% efficiency
- The nanofiber dressings release the compounds for over 28 days, providing sustained exposure
- Co‑delivery dramatically increases LL‑37 gene expression in immune cells and skin, outperforming free vitamin D3 or single‑agent dressings
Practical Outcomes
- The study shows a promising way to enhance wound healing by locally boosting LL‑37, but making the nanofiber dressings requires specialized equipment. For DIY enthusiasts, the concept suggests that topical vitamin D3 combined with a CYP24A1 blocker could be explored, though safe, effective formulations are not yet available for home use.
Summary
Scientists made a special wound dressing that slowly releases vitamin D3 and a drug that blocks its breakdown, which together boost the body’s own antimicrobial peptide LL‑37. In lab tests and mouse skin, this combo dramatically raised LL‑37 levels and helped fight infections better than using vitamin D3 alone.
Abstract
Surgical site infections represent a significant clinical problem. Herein, we report a nanofiber dressing for topical codelivery of immunomodulating compounds including 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) and VID400, a <i>CYP24A1</i> inhibitor in a sustained manner, for inducing the expression of the endogenous cathelicidin antimicrobial peptide (<i>CAMP</i>) gene encoding the hCAP18 protein, which is processed into the LL-37 peptide. Nanofiber wound dressings with coencapsulation of 1,25(OH)<sub>2</sub>D<sub>3</sub> and VID400 were generated by electrospinning. Both 1,25(OH)<sub>2</sub>D<sub>3</sub> and VID400 were coencapsulated into nanofibers with loading efficiencies higher than 90% and exhibited a prolonged release from nanofiber membranes longer than 28 days. Incubation with 1,25(OH)<sub>2</sub>D<sub>3</sub>/VID400-coencapsulated poly(ϵ-caprolactone) nanofiber membranes greatly induced the hCAP18/LL-37 gene expression in monocytes, neutrophils, and keratinocytes in vitro. Moreover, the administration of 1,25(OH)<sub>2</sub>D<sub>3</sub>/VID400-coencapsulated nanofiber membranes dramatically promoted the hCAP18/LL-37 expression in dermal wounds created in both human <i>CAMP</i> transgenic mice and human skin tissues. The 1,25(OH)<sub>2</sub>D<sub>3</sub>- and VID400-coencapsulated nanofiber dressings enhanced innate immunity via the more effective induction of antimicrobial peptide than the free drug alone or 1,25(OH)<sub>2</sub>D<sub>3</sub>-loaded nanofibers. Together, 1,25(OH)<sub>2</sub>D<sub>3</sub>/VID400-embedded nanofiber dressings presented in this study show potential in preventing surgical site infections.
Study Information
pubmed
2022
2022-02-18T00:00:00.000Z
10.1021/acs.molpharmaceut.1c00944
7
30