Abstract
Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds.
Highlights
The number of antibiotic resistant bacteria, as well as the number of immune deficient patients, is increasing
Chronic wounds are often associated with microbial biofilms, i.e., organized communities of one or more microorganism species encased and shielded by extracellular polymeric substances [5,6]
The low concentrations of antibiotics that reach the bacteria in the biofilm favor the formation of persisters, i.e., physiologically inactive dormant cells that are less responsive to antibiotics [9]
Summary
The number of antibiotic resistant bacteria, as well as the number of immune deficient patients, is increasing. A ciprofloxacin base was chosen as model drug because of its low water-solubility, detectability using fluorescence spectroscopy, and quorum sensing inhibiting properties in Pseudomonas aeruginosa (P. aeruginosa) at concentrations below the minimal inhibitory concentration (MIC) [12] It is a broad-spectrum antibiotic that has been approved by the U.S Food and Drug Administration (FDA) for the treatment of urinary tract and other infections, including skin and skin-structure infections. Human skin infection models are Pharmaceutics 2019, 11, 527 realistic animal-free systems; even if they cannot completely replace in vivo studies, they are useful tools to screen antimicrobial formulations [26]. Using this model, we could measure the drug delivery kinetics, monitor eventual toxic effects, and measure the antimicrobial activity of the tested materials
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