Syringeable Pluronic-α-cyclodextrin supramolecular gels for sustained delivery of vancomycin

Abstract

The ability of Pluronic® F127 to form supramolecular gels in the presence of αCD has been explored as a way to design syringeable gel formulations able to sustain drug release while using the lowest proportion of both components. The effects of αCD concentration range (0-9.7% w/v) in copolymer (6.5%, 13% and 20%) gel features were evaluated at 4, 20 and 37°C. An effective complexation of Pluronic and αCD was evidenced as a change in the surface pressure of the π-A isotherm of Pluronic on a subphase of CD solution and the apparition of new peaks in the X-ray spectra. Once the Pluronic and αCD solutions were mixed, the systems became progressively turbid solutions or white gels. The greater the αCD concentration was, the faster the gel formation. The supramolecular hydrogels were thixotropic and those containing 5% or more αCD had G' values above G″ at room temperature, but they were still easily syringeable. The values of both moduli increased as temperature raised; the effect being more evident for 13% and 20% w/v copolymer. The gels prepared with low proportions of αCD exhibited phase separation in few days, particularly when stored at 4 or 37 °C. By contrast, those prepared with 6.5% copolymer were stable for at least two months when stored at 20 °C. The gels were able to sustain vancomycin release for several days; the higher the αCD proportion, the slower the release was. Furthermore, the drug-loaded gels showed activity against Staphylococcus aureus. The results obtained highlight the role of the αCD concentration on the tuning of the rheological features and drug release profiles from Pluronic gels.