Bioinspired Imprinted PHEMA-Hydrogels for Ocular Delivery of Carbonic Anhydrase Inhibitor Drugs

Abstract

Hydrogels with high affinity for carbonic anhydrase (CA) inhibitor drugs have been designed trying to mimic the active site of the physiological metallo-enzyme receptor. Using hydroxyethyl methacrylate (HEMA) as the backbone component, zinc methacrylate, 1- or 4-vinylimidazole (1VI or 4VI), and N-hydroxyethyl acrylamide (HEAA) were combined at different ratios to reproduce in the hydrogels the cone-shaped cavity of the CA, which contains a Zn(2+) ion coordinated to three histidine residues. 4VI resembles histidine functionality better than 1VI, and, consequently, pHEMA-ZnMA(2) hydrogels bearing 4VI moieties were those with the greatest ability to host acetazolamide or ethoxzolamide (2 to 3 times greater network/water partition coefficient) and to sustain the release of these antiglaucoma drugs (50% lower release rate estimated by fitting to the square root kinetics). The use of acetazolamide as template during polymerization did not enhance the affinity of the network for the drugs. In addition to the remarkable improvement in the performance as controlled release systems, the biomimetic hydrogels were highly cytocompatible and possessed adequate oxygen permeability to be used as medicated soft contact lenses or inserts. The results obtained highlight the benefits of mimicking the structure of the physiological receptors for the design of advanced drug delivery systems.

Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

“…Prolonged release on the corneal surface of hydrophilic drugs might be better achieved by means of contact lenses or hydrogel films that bear functional moieties suitable for interacting with the drug molecules [15]. Thus, compared with the biomimetic/imprinted contact lenses [15,50], poloxamine micelles may offer higher initial levels of ETOX at the lachrymal fluid; the greater concentration gradient facilitating the passing through the cornea of this high permeability drug. Subsequent application of ETOX-medicated contact lenses may enable the attainment of long-term drug levels.…”

“…On the other hand, it was shown that ETOX can be solubilized by forming inclusion complexes with cyclodextrin derivatives and that topically active formulations which combine ETOX and timolol can be thus prepared [13,14]. More recently, biomimetic contact lenses capable of loading ETOX and of controlling the drug release were prepared with the intention of prolonging the contact time between the drug and the eye and enhancing the ocular bioavailability [15].…”

Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses

“…Many methods have been developed to modify the conventional contact lenses to improve their drug loading and release (16,52,(60)(61)(62)(63)(64)(65). The use of a device from which a drug may diffuse can improve the contact time of the drug with its target tissue.…”

Contact lenses as drug controlled release systems: a narrative review

“…Vitamin E loading proved to be very effective in increasing release duration of lidocaine, CyA, timolol, levofloxacin, chlorhexidine, dorzolamine, dexpantenol, betaine, dexamethasone and betamethasone, from hours to several days. [32][33][34][35][36][37] Research on dry eye management has been increasingly focusing on the inflammatory aspect and CyA was FDA approved to treat moderate-to-severe dry eye disease. SHCLs were able to keep CyA delivery rates within therapeutic levels for 14 days.…”