title: Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery and Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Jiang
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.forename: Franklin D
authors.initials: FD
authors.lastname: Shuler
authors.forename: Chi-Hwa
authors.initials: CH
authors.lastname: Wang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xie
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D002112:Calcifediol / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D020298:U937 Cells; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D003692:Delayed-Action Preparations; D011091:Polyesters; C016240:polycaprolactone; C033616:poly(lactide); D002112:Calcifediol; D054804:Cathelicidins