Codelivery of 1α,25-Dihydroxyvitamin D3and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction

Yajuan Su, Gitali Ganguli-Indra, Nilika Bhattacharya, Isabelle E. Logan, Arup K. Indra, Adrian F. Gombart, Shannon L. Wong, Jingwei Xie

Research output: Contribution to journalArticlepeer-review

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 D3(1,25(OH)2D3) and VID400, a CYP24A1 inhibitor in a sustained manner, for inducing the expression of the endogenous cathelicidin antimicrobial peptide (CAMP) gene encoding the hCAP18 protein, which is processed into the LL-37 peptide. Nanofiber wound dressings with coencapsulation of 1,25(OH)2D3and VID400 were generated by electrospinning. Both 1,25(OH)2D3and 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)2D3/VID400-coencapsulated poly(μ-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)2D3/VID400-coencapsulated nanofiber membranes dramatically promoted the hCAP18/LL-37 expression in dermal wounds created in both human CAMP transgenic mice and human skin tissues. The 1,25(OH)2D3- 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)2D3-loaded nanofibers. Together, 1,25(OH)2D3/VID400-embedded nanofiber dressings presented in this study show potential in preventing surgical site infections.

Original languageEnglish (US)
Pages (from-to)974-984
Number of pages11
JournalMolecular Pharmaceutics
Volume19
Issue number3
DOIs
StatePublished - Mar 7 2022
Externally publishedYes

Keywords

  • 1α,25-dihydroxyvitamin D3
  • CYP24A1 inhibitor
  • antimicrobial peptide LL-37
  • codelivery
  • nanofiber dressings

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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