Design of infection-resistant antibiotic-releasing polymers. II. Controlled release of antibiotics through a plasma-deposited thin film barrier.
In the first paper in this series, we described the methods to synthesize an antibacterial polyurethane (PU) incorporating ciprofloxacin as the releasable antibiotic and poly(ethylene glycol) as the pore-forming agent. Here, we report that a thin, RF-plasma-deposited, n-butyl methacrylate (BMA) overlayer on this drug-loaded PU can act as a rate-limiting barrier to achieve a constant, sustained release of ciprofloxacin. Deposition power and deposition time during the coating process were optimized to give an appropriate crosslinked coating barrier that yielded desirable release rates, above the minimum required killing rate, N(kill). Electron spectroscopy for chemical analysis (ESCA), also known as X-ray photoelectron spectroscopy (XPS), was used to characterize the coating, and its crosslinking degree was indirectly related to the C/O ratio. Increasing either deposition power (10-60 W) or duration (5-25 min) resulted in increased C/O ratios and decreased ciprofloxacin release rates. The correlation between increased C/O ratios and reduced release rates is believed to be due to the increased crosslinking, increased hydrophobicity and increased thickness of the coating. The optimal plasma conditions to attain an appropriate crosslinked plasma-deposited film (PDF) required argon etching, pre-treatment of the matrices with an 80W-BMA plasma for 1 min, followed by immediate BMA plasma deposition at 40 W and 150 mT for 20 min. By using these plasma deposition protocols, we eliminated the initial burst effect, significantly reduced the release rates, and closely approached the zero order release kinetics for at least five days. In this study, we also showed that ESCA could be used as a powerful tool to explain the release behavior of molecules through the plasma-deposited films (PDFs).
Kwok
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Departments of Chemical Engineering and Bioengineering, Box 351720, University of Washington, Seattle 98195, USA.
Horbett
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Ratner
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D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001128:Argon / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D008689:Methacrylates / Q000737:chemistry*; D012995:Solubility; D013052:Spectrometry, X-Ray Emission; D013499:Surface Properties; D013997:Time Factors
D000890:Anti-Infective Agents; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D008689:Methacrylates; D002939:Ciprofloxacin; D001128:Argon; C016284:butyl methacrylate