Ciprofloxacin loaded vascular prostheses functionalized with poly-methylbeta- cyclodextrin: The importance of in vitro release conditions

• Published in: Journal of drug delivery science and technology 2019-10, Vol.53, p.101166, Article 101166
• Main Authors: Garcia-Fernandez, M.J., Maton, M., Benzine, Y., Tabary, N., Baptiste, E. Jean, Gargouri, M., Bria, M., Blanchemain, N., Karrout, Y.
• Format: Article
• Language: English
• Subjects: Ciprofloxacin; Controlled drug delivery; Diffusion test; Modified flow-through cell; PET-MeβCD; Poly-MeβCD; Vascular prostheses
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2019.101166

Synthetic Vascular Graft Infection (SVGI) can be very serious for patients with dramatic consequences (up to 6%). Polyester vascular grafts (PET) were modified with polymerized cyclodextrin (Poly-MeβCD) and loaded with ciprofloxacin (CFX) for the prevention of postoperative infections. The aim of this study was to investigate the CFX/Poly-MeβCD interactions and the importance of the type of the dissolution technique. The solubility of CFX was significantly improved upon Poly-MeβCD, and the interaction between CFX and Poly-MeβCD were observed by NMR (Nuclear Magnetic Resonance). Drug release was measured in phosphate buffer saline pH 7.4 at 37 °C using: (i) agitated flasks, (ii) the paddle apparatus, (iii) the conventional flow-through cells, (iv) the modified flow-through cells with agarose gel at different flow rates. Importantly, CFX release depends on the flow rate as well as the experimental set-up in vitro. CFX release from virgin prostheses (PET) was faster than from functionalized prostheses (PET-MeβCD), irrespective of the flow rate, which indicates the superiority of Poly-MeβCD in the control of CFX release. The CFX diffusion from PET-MeβCD into agarose gel showed a continuously progressive diffusion during 7 days. Thus, this test can be highly appropriate for in vitro characterization of such drug delivery systems. [Display omitted]