Moxifloxacin imprinted silicon based hydrogels for sustained ocular release

Abstract

Introduction: Traditional eye drop formulations are poorly efficient for ocular drug delivery, mainly due to the low residence time of the drug on the eye which results in a low bioavailability (1–5%) [1]. Soft contact lenses (SCLs) could overcome the rapid clearance of the drug in the eye. However, their insufficient capacity as drug reservoir may prevent the release of therapeutic concentrations [2]. Drug imprinted hydrogels have shown an increase in drug uptake and prolonged drug release [3]. In this work imprinted and non-imprinted silicon based hydrogels were designed for the loading of the antibiotic drug moxifloxacin hydrochloride (MXF) and evaluated regarding their potential use as therapeutic SCLs.

Materials and methods: A silicon based (TRIS) hydrogel was prepared as previously reported [4]. An alternative composition containing acrylic acid, a functional monomer that may establish potential interactions with MXF was also prepared (TRIS/AA). A molecular imprinting strategy for MXF was followed and materials containing the drug were also synthesized (TRIS + D and TRIS/AA + D). After extensive washing, all hydrogels were loaded with the drug by soaking in MFX solution (2.5 mg/mL) at room temperature for 72 h. Release kinetics was investigated under sink conditions in NaCl solution. Transmittance, swelling and oxygen permeability were recorded. A mathematical model was applied to predict the in vivo efficacy of the drug release profile.

Results: All hydrogels showed adequate physical properties for daily contact lenses wearing. No significant variations were observed in the release profile between TRIS + D and TRIS/AA hydrogels, while TRIS hydrogels showed faster release. The TRIS/AA + D hydrogel provided the most sustained release. The MXF concentration profile in the tear fluid estimated from the mathematical model indicated that the release of MXF from TRIS/AA + D hydrogel may be above the minimal inhibitory concentration (MIC) of different microorganisms typically colonizers of the eye for 48 h, while TRIS + D hydrogel was capable of maintaining the necessary concentration of MXF for ≈24 h and the non-imprinted hydrogels for ≈ 10 h.

Discussion and conclusions: Imprinted silicone hydrogels bearing AA functional mers were demonstrated to be able to host large amount of MXF and to provide controlled release. These imprinted materials could be useful for the design of daily therapeutic SCLs.

Acknowledgements

To Fundação para a Ciência e a Tecnologia for Diana Silva PhD Grant (PD/BD/114088/2015), and for funding through the project PTDC/CTM-BIO/3640/2014.