Poly-(cyclo)dextrins as ethoxzolamide carriers in ophthalmic solutions and in contact lenses

• Published in: Carbohydrate polymers Vol. 98; no. 2; pp. 1343 - 1352
• Main Authors: García-Fernández, M.J., Tabary, N., Martel, B., Cazaux, F., Oliva, A., Taboada, P., Concheiro, A., Alvarez-Lorenzo, C.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 06.11.2013; Elsevier
• Subjects: Acrylic hydrogel; Applied sciences; Biological and medical sciences; carbonate dehydratase; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; citric acid; Citric Acid - chemistry; Contact Lenses; Cross-Linking Reagents - chemistry; Cyclodextrin polymer; Cyclodextrins - chemistry; Delayed-Action Preparations - chemical synthesis; Drug Carriers - chemical synthesis; drugs; Ethoxzolamide - chemistry; Ethoxzolamide - pharmacology; Ethoxzolamide solubilization; Exact sciences and technology; Eye; gamma-cyclodextrin; Glaucoma; hydrophilic polymers; Hydrophobic and Hydrophilic Interactions; Inclusion complex; maltodextrins; Medical sciences; Methacrylates - chemistry; Natural polymers; Ophthalmic Solutions - chemistry; Ophthalmic Solutions - pharmacology; oral administration; Pharmacology. Drug treatments; Physicochemistry of polymers; Polymerization; Solubility; Starch and polysaccharides; Sustained release; therapeutics; Glaucoma; Cyclodextrin polymer; Sustained release; Ethoxzolamide solubilization; Acrylic hydrogel; Inclusion complex; Biological properties; Antiglaucomatous agent; Cytotoxicity; Drug carrier; Solubilization; Hydroxyethyl methacrylate polymer; Crosslinked polymer; Water solubility; Release; Contact lens; Control release polymer; Crosslinking; In vitro; Citric acid; Cyclodextrin; Preparation; Oside polymer; Kinetics; Aqueous solution
• DOI: 10.1016/j.carbpol.2013.08.003
• ISSN: 0144-8617

•Water soluble poly(cyclo)dextrins notably enhanced ethoxzolamide solubility.•Poly(cyclo)dextrins strongly delayed drug diffusion compared to free cyclodextrins.•Poly(cyclo)dextrins showed good ocular compatibility in HET-CAM test.•Suitable tool for enhanced drug loading and control of drug release in contact lenses. Efficient ophthalmic therapy requires the development of strategies that can provide sufficiently high drug levels in the ocular structures for a prolonged time. This work focuses on the suitability of poly-(cyclo)dextrins as carriers able to solubilize the carbonic anhydrase inhibitor (CAI) ethoxzolamide (ETOX), which is so far used for oral treatment of glaucoma. Topical ocular treatment should notably enhance the efficiency/safety profile of the drug. Natural α-, β- and γ-cyclodextrins and a maltodextrin were separately polymerized using citric acid as cross-linker agent under mild conditions. The resultant hydrophilic polymers exhibited larger capability to solubilize ETOX than the pristine (cyclo)dextrins. Moreover, they provided sustained drug diffusion in artificial lachrymal fluid. Interestingly the poly-(cyclo)dextrins solutions facilitate the loading of remarkably high doses of ETOX in poly(2-hydroxyethyl methacrylate)-based contact lenses. Exploiting ionic interactions between functional groups in the contact lenses and remnant free carboxylic acids in the citric acid linkers of poly-(cyclo)dextrins led to the retention of the drug-loaded poly-(cyclo)dextrins and, in turn, to sustained release for several weeks.