Poly-(cyclo)dextrins as ethoxzolamide carriers in ophthalmic solutions and 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.
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
M J
MJ
García-Fernández
N
N
Tabary
B
B
Martel
F
F
Cazaux
A
A
Oliva
P
P
Taboada
A
A
Concheiro
C
C
Alvarez-Lorenzo
D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D019343:Citric Acid / Q000737:chemistry; D003261:Contact Lenses; D003432:Cross-Linking Reagents / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis*; D004337:Drug Carriers / Q000138:chemical synthesis*; D005016:Ethoxzolamide / Q000737:chemistry* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates / Q000737:chemistry; D009883:Ophthalmic Solutions / Q000737:chemistry* / Q000494:pharmacology; D058105:Polymerization; D012995:Solubility
D002257:Carbonic Anhydrase Inhibitors; D003432:Cross-Linking Reagents; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008689:Methacrylates; D009883:Ophthalmic Solutions; D019343:Citric Acid; C005044:hydroxyethyl methacrylate; D005016:Ethoxzolamide
Acrylic hydrogel; Cyclodextrin polymer; Ethoxzolamide solubilization; Glaucoma; Inclusion complex; Sustained release