Diclofenac sustained release using an LbL coated silicon based hydrogel

Abstract

Introduction: Eye drops remain the primary dosage form for ocular therapy because of the easiness of administration by the patient, but they provide low drug bioavailability [1]. Soft contact lenses have been evaluated for several decades as potential drug vehicles for ocular therapy. Nevertheless, their usual low drug uptake prevents the achievement of therapeutic levels [2]. An approach to overcome some limitations of contact lenses is to use the layer-by-layer (LbL) method to form a surface barrier that regulates drug release within the therapeutic window. The main objective of this work was to develop LBL coated therapeutic lenses loaded with the anti-inflammatory drug diclofenac (DCF).

Materials and methods: A silicon based hydrogel material (TRIS) was synthesized, loaded with sodium diclofenac (DCF) and coated with different polyelectrolytes by the LbL method. The polyelectrolytes alginate (ALG), chitosan (CHI) and hyaluronic acid (HA) were chosen and genipin was used as cross-linking agent. The coating consisted in a triple layer of ALG/CHI/HA. DCF release kinetics was evaluated in sink conditions in NaCl solution. Uncoated and coated hydrogels were submitted to the chorioallantoic membrane test (HET-CAM test) for potential ocular irritation. The hydrogel-lachrymal protein (lysozyme) interaction was evaluated by quartz-crystal microbalance with dissipation (QCM-D). Transmittance and oxygen permeability were studied. A mathematical model was used to estimate the in vivo efficacy of the coated lenses.

Results: The coating allowed a controlled release of DCF, while maintaining the required properties for daily contact lens application. Both uncoated and coated hydrogels successfully passed the HET-CAM test. QCM-D data revealed the stability of the layers and some antifouling activity of the coating against lysozyme. The effective diffusion of DCF through the samples was calculated: lower diffusivity was found for the coated hydrogels (1.9 ± 0.7e⁻¹³ m²/s) compared to the uncoated (8.6 ± 1.1e⁻¹³ m²/s). The mathematical modelling appoint to a significant difference between the samples: by admitting the half maximal inhibitory concentration (IC₅₀) of DCF, an estimated 200% increase in the predicted in vivo efficiency was obtained due to the presence of the coating.

Discussion and conclusions: The coated hydrogel presents adequate characteristics to be used in therapeutic contact lenses, concerning the evaluated properties. DCF released was significantly enhanced by the presence of the coating, showing favourable kinetics due to the interactions between the polyelectrolytes and the drug. The applied mathematical model revealed a sustainable release of DCF within the therapeutic window for two weeks.

Acknowledgements

The authors thank 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.