1α,25-dihydroxyvitamin D3-eluting nanofibrous dressings induce endogenous antimicrobial peptide expression

Jiang Jiang; Yang Zhang; Arup K Indra; Gitali Ganguli-Indra; Mai N Le; Hongjun Wang; Ronald R Hollins; Debra A Reilly; Mark A Carlson; Richard L Gallo; Adrian F Gombart; Jingwei Xie

doi:10.2217/nnm-2018-0011

1α,25-dihydroxyvitamin D₃-eluting nanofibrous dressings induce endogenous antimicrobial peptide expression

Nanomedicine (Lond). 2018 Jun;13(12):1417-1432. doi: 10.2217/nnm-2018-0011. Epub 2018 Jul 4.

Authors

Jiang Jiang¹, Yang Zhang^{2

3}, Arup K Indra^{2

4

5

6}, Gitali Ganguli-Indra^{4

6}, Mai N Le⁴, Hongjun Wang¹, Ronald R Hollins⁷, Debra A Reilly⁷, Mark A Carlson^{8

9}, Richard L Gallo¹⁰, Adrian F Gombart^{2

3}, Jingwei Xie¹

Affiliations

¹ Department of Surgery, Transplant & Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA.
² Department of Biochemistry & Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
³ Nutrition Graduate Program, School of Biological & Population Health Sciences, College of Public Health & Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
⁴ Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
⁵ Department of Dermatology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA.
⁶ Knight Cancer Institute, OHSU, Portland, OR 97239, USA.
⁷ Department of Surgery - Plastic & Reconstructive Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA.
⁸ Department of Surgery - General Surgery & Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
⁹ Department of Surgery, VA Nebraska - Western Iowa Health Care System, Omaha, NE 68105, USA.
¹⁰ Department of Dermatology, University of California, San Diego, CA 92093, USA.

Abstract

Aim: The aim of this study was to develop a nanofiber-based dressing capable of local sustained delivery of 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) and augmenting human CAMP induction.

Materials & methods: Nanofibrous wound dressings containing 1,25(OH)₂D₃ were successfully prepared by electrospinning, which were examined in vitro, in vivo and ex vivo.

Results: 1,25(OH)₂D₃ was successfully loaded into nanofibers with encapsulation efficiency larger than 90%. 1,25(OH)₂D₃ showed a sustained release from nanofibers over 4 weeks. Treatment of U937 and HaCaT cells with 1,25(OH)₂D₃-loaded poly(ϵ-caprolactone) nanofibers significantly induced hCAP18/LL37 expression in monocytes and keratinocytes, skin wounds of humanized transgenic mice and artificial wounds of human skin explants.

Conclusion: 1,25(OH)₂D₃ containing nanofibrous dressings could enhance innate immunity by inducing antimicrobial peptide production.

Keywords: 1α,25-dihydroxyvitamin D3; antimicrobial peptides LL-37; electrospun nanofibers; endogenous production; innate immunity; sustained delivery.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Infective Agents / administration & dosage*
Anti-Infective Agents / chemistry
Antimicrobial Cationic Peptides / chemistry
Antimicrobial Cationic Peptides / metabolism*
Bandages / microbiology
Cell Line
Humans
Keratinocytes / drug effects
Keratinocytes / microbiology
Mice
Mice, Transgenic
Monocytes / drug effects
Nanofibers / administration & dosage*
Nanofibers / chemistry
Vitamin D / administration & dosage
Vitamin D / analogs & derivatives*
Vitamin D / chemistry
Wound Closure Techniques

Substances

Anti-Infective Agents
Antimicrobial Cationic Peptides
dihydroxy-vitamin D3
Vitamin D

Abstract

Publication types

MeSH terms

Substances

Grants and funding