Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides

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• 作者：Jiang Jiang ; Guojun Chen ; Franklin D. Shuler ; Chi-Hwa Wang…
• 关键词：25 ; hydroxyvitamin D3 ; electrospinning ; fibers ; local sustained delivery ; surgical site infection
• 刊名：Pharmaceutical Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：32
• 期：9
• 页码：2851-2862
• 全文大小：5,009 KB
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• 作者单位：Jiang Jiang (1)
  Guojun Chen (2)
  Franklin D. Shuler (3)
  Chi-Hwa Wang (4)
  Jingwei Xie (1)
  
  1. Department of Surgery and Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA
  2. Bruker Nano Surface Division, Santa Barbara, California, 93117, USA
  3. Department of Orthopaedic Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, 25755, USA
  4. Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Pharmacy
  Biochemistry
  Medical Law
  Biomedical Engineering
  
• 出版者：Springer Netherlands
• ISSN：1573-904X

文摘

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.