Local Sustained Delivery of 25-Hydroxyvitamin D<inf>3</inf> for Production of Antimicrobial Peptides

Jiang Jiang, Guojun Chen, Franklin D. Shuler, Chi Hwa Wang, Jingwei Xie

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Abstract Purpose: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D<inf>3</inf> to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods: 25-hydroxyvitamin D<inf>3</inf> loaded poly(<inf>L</inf>-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D<inf>3</inf> releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. Results: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D<inf>3</inf>. The duration of 25-hydroxyvitamin D<inf>3</inf> release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D<inf>3</inf>. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D<inf>3</inf> loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions: Plasma treated and 25-hydroxyvitamin D<inf>3</inf> loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity.

Original languageEnglish (US)
Article number1667
Pages (from-to)2851-2862
Number of pages12
JournalPharmaceutical Research
Volume32
Issue number9
DOIs
StatePublished - Sep 8 2015

Fingerprint

Calcifediol
Peptides
Fibers
Monocytes
Immunosorbents
Keratinocytes
Plasmas
Assays
Microscopes
Enzyme-Linked Immunosorbent Assay
U937 Cells
Electrospinning
Enzymes
Cytotoxicity
Encapsulation
Pseudomonas aeruginosa
Fluorescent Antibody Technique
Bacteria
Electron microscopes
Electrons

Keywords

  • 25-hydroxyvitamin D<inf>3</inf>
  • electrospinning
  • fibers
  • local sustained delivery
  • surgical site infection

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

Cite this

Local Sustained Delivery of 25-Hydroxyvitamin D<inf>3</inf> for Production of Antimicrobial Peptides. / Jiang, Jiang; Chen, Guojun; Shuler, Franklin D.; Wang, Chi Hwa; Xie, Jingwei.

In: Pharmaceutical Research, Vol. 32, No. 9, 1667, 08.09.2015, p. 2851-2862.

Research output: Contribution to journalArticle

Jiang, Jiang ; Chen, Guojun ; Shuler, Franklin D. ; Wang, Chi Hwa ; Xie, Jingwei. / Local Sustained Delivery of 25-Hydroxyvitamin D<inf>3</inf> for Production of Antimicrobial Peptides. In: Pharmaceutical Research. 2015 ; Vol. 32, No. 9. pp. 2851-2862.
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abstract = "Abstract Purpose: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods: 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. Results: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions: Plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity.",
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AU - Jiang, Jiang

AU - Chen, Guojun

AU - Shuler, Franklin D.

AU - Wang, Chi Hwa

AU - Xie, Jingwei

PY - 2015/9/8

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N2 - Abstract Purpose: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods: 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. Results: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions: Plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity.

AB - Abstract Purpose: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods: 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. Results: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions: Plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity.

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KW - fibers

KW - local sustained delivery

KW - surgical site infection

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