Therapeutic contact lenses: layer-by-layer coatings and molecular imprinting as strategies for drug delivery control

Diana Cristina Morais da Silva Pereira

Key information

Authors:

Diana Cristina Morais da Silva Pereira (Diana Cristina Morais da Silva)

Supervisors:

Hermínio José Cipriano de Sousa; Ana Paula Valagão Amadeu do Serro (Ana Paula Valagão Amadeu do Serro); Benilde de Jesus Vieira Saramago (Benilde de Jesus Vieira Saramago)

Published in

June 26, 2020

Abstract

The use of drug-loaded ophthalmic lenses has been regarded as an adequate solution to overcome the main disadvantages of conventional topical ocular treatments. In fact, therapeutic soft contact lenses (SCLs) may ensure a higher bioavailability of the drug in the eye, minimizing its wastage and side effects, and avoiding the frequent and regular instillation of eyedrops, which may be compromised by poor patients’ compliance. However, to be efficient, the SCLs must ensure a sustained release of adequate amounts of drug. The present thesis focused on two strategies to control the release of ophthalmic drugs: surface modification through layer-by-layer (LbL) assembly and molecular imprinting. Different LbL coatings, prepared using natural based polyelectrolytes (e.g. alginate (ALG), chitosan (CHI), poly-L-lysine (PLL) and hyaluronate (HA)), were deposited on a lab-made silicone-based hydrogel (TRIS/NVP/HEMA), a commercial silicone hydrogel for SCLs (Definitive 50), and two commercially available SCLs (SofLens and Purevision). The produced coatings were effective only in the control of the release of diclofenac (DCF), but had no effect on the releases of ketorolac (KETO), chlorhexidine (CHX) and moxifloxacin (MXF). The specificity of the barrier effect of these LbL coatings for DCF was attributed to the unique interactions between the polyelectrolytes and DCF (e.g. electrostatic interactions, H-bonds). Furthermore, some of the LbL coatings demonstrated antifouling and antibacterial properties, and were able to withstand high hydrostatic pressure (HHP) sterilization. To overcome the inability of the LbL coatings to sustain the release of MXF, the TRIS/NVP/HEMA was submitted to molecular imprinting of the drug associated with the addition of a functional monomer (acrylic acid). The results showed a 6-fold increase in the amount of drug released. The conjugation of the most promising LbL coating with the molecular imprinting technique allowed a sustained dual release of DCF+MXF from TRIS/NVP/HEMA. The release profiles obtained under hydrodynamic conditions demonstrated that DCF concentration remained above the IC50 values of COX-1 and COX-2 for 9 days and that MXF concentration remained above the MICs of S. aureus and S. epidermidis for more than 10 days. The samples were biocompatible, did not induce ocular irritancy, demonstrated antifouling behaviour and kept suitable physical properties. Thus, they seem suitable for therapeutic SCLs application.