title: Cyclodextrin complexation highly enhances efficacy of arylsulfonylureido benzenesulfonamide carbonic anhydrase inhibitors as a topical antiglaucoma agents.
abstract: Two new sulfonamides incorporating arylsulfonylureido moieties were complexed with gamma cyclodextrin (γ-CD), hydroxypropyl-gamma cyclodextrin (HPγ-CD), hydroxypropyl-beta cyclodextrin (HPβ-CD) and hydroxyethyl-beta cyclodextrin (HEβ-CD) in order to obtain drug formulations with effective topical intraocular pressure (IOP) lowering effects, in an animal model of glaucoma. The HPγ-CD was the best solubilizing agent for the two sulfonamides and its complexes were characterized in detail and administered to rabbits with eye hypertension of 45-50 mmHg. The peak IOP lowering was observed after 1h post-administration and was of 36-37 mmHg. A low IOP pressure (of around-35 mmHg) was then maintained for the next 24h post-administration, which has not been observed before with any IOP lowering drug.
authors: Università degli Studi di Firenze, Dipartimento di Chimica, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy.
authors: Marco
authors: M
authors: Bragagni
authors: Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors: Murat
authors: M
authors: Bozdag
authors: Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors: Fabrizio
authors: F
authors: Carta
authors: Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors: Andrea
authors: A
authors: Scozzafava
authors: Università degli Studi di Firenze, Dipartimento NEUROFARBA, Sezione di Farmacologia, Viale Pieraccini 6, 50139 Florence, Italy.
authors: Cecilia
authors: C
authors: Lanzi
authors: Università degli Studi di Firenze, Dipartimento NEUROFARBA, Sezione di Farmacologia, Viale Pieraccini 6, 50139 Florence, Italy.
authors: Emanuela
authors: E
authors: Masini
authors: Università degli Studi di Firenze, Dipartimento di Chimica, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy.
authors: Paola
authors: P
authors: Mura
authors: Università degli Studi di Firenze, Dipartimento NEUROFARBA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry*; D004195:Disease Models, Animal; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D011817:Rabbits; D012995:Solubility; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000096926:Benzenesulfonamides
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D003505:Cyclodextrins; D013449:Sulfonamides; D000096926:Benzenesulfonamides
keywords: Antiglaucoma agent; Carbonic anhydrase; Cyclodextrin complexation; Isoforms I, II, IX, XII; Sulfonamide