Citicoline eluting hydrogels for therapeutic contact lenses intended to treat neurodegenerative diabetic ocular diseases

Abstract

Ophthalmic neurodegenerative diseases related to diabetes, such as glaucoma and retinopathy, are among the major causes of blindness in the world. Citicoline (CIT) in the form of eye drops is currently used for the treatment/prevention of these diseases, which affect the posterior segment of the eye. To ensure the drug penetration into the back of the eye, frequent instillations of highly concentrated drug solutions are required with potential side effects. Drug-loaded soft contact lenses (SCLs) may be an effective alternative to the conventional eye drop treatment, since they may enable a sustained drug release during daily wear, ensuring a higher drug bioavailability, and avoiding drug waste. In this work, one 2-hydroxyethyl methacrylate (HEMA) based hydrogel was functionalised with N-(3-aminopropyl) methacrylamide hydrochloride (APMA), molecularly imprinted with CIT and loaded with the same drug. The material was extensively characterised, in terms of morphology, optical, mechanical, and physical–chemical properties, namely, equilibrium water content, wettability, oxygen and ionic permeability, Young’s modulus, shear deformation, transmittance and refractive index, before and after steam sterilisation. Additionally, the tendency of the material to adsorb proteins of the lachrymal fluid was evaluated and its biocompatibility was assessed by irritation and cytotoxicity assays. Comparison with the non-functionalised and non-imprinted hydrogel showed that the modified hydrogel led to a sustained in vitro release of a much higher amount of CIT than the original one, while keeping typical values for physical–chemical properties of SCLs. The drug-loaded material resisted steam sterilisation and proved to be biocompatible, demonstrating adequate properties to be used in therapeutic SCLs for the prophylaxis/treatment of neurodegenerative diabetic ocular diseases. The neuroprotective effect of the released drug was confirmed with tests using porcine retinal explants.