title: Thiolated α-Cyclodextrin: The Invisible Choice to Prolong Ocular Drug Residence Time.
abstract: It was the aim of this study to develop cysteamine-conjugated α-cyclodextrin (α-CD) enabled to form disulfide bonds with cysteine-rich substructures of the ocular mucus layer to provide a prolonged residence time of incorporated drugs at the site of action. Cysteamine was covalently attached to oxidized α-CD via reductive amination. The resulting α-CD-cysteamine conjugates (α-CD-Cys) were characterized regarding the amount of free thiol groups attached to the oligomer backbone via Ellman's reagent; resazurin assay was conducted for cytotoxicity, and mucoadhesive properties were evaluated on porcine intestinal and ocular mucosal tissues. Furthermore, albino rabbits were used for assessing the irritation-masking effects of α-CD-Cys. Free thiol groups attached to the backbone were in the range of 558 ± 24-1143 ± 92 μmol/g. None of these α-CD-Cys unduly affected the viability of Caco-2 cells in a concentration of 0.5%. Mucoadhesive properties of α-CD-Cys were up to 32-fold improved compared to unmodified α-CD. Encapsulation of cetirizine into α-CD-Cys resulted in significantly reduced local ocular mucosal irritation of this model drug. According to these results, α-CD-Cys is a promising new tool to prolong drug residence time on the ocular mucosal surface.
authors.affiliation: Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ijaz
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University Bahawalpur, Bahawalpur, Pakistan.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University Bahawalpur, Bahawalpur, Pakistan.
authors.forename: Naveed
authors.initials: N
authors.lastname: Akhtar
authors.affiliation: Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
authors.forename: Flavia
authors.initials: F
authors.lastname: Laffleur
authors.affiliation: Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000269:Adhesives; D060433:Administration, Ophthalmic; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival; D017332:Cetirizine / Q000008:administration & dosage / Q000493:pharmacokinetics; D003315:Cornea / Q000378:metabolism; D003543:Cysteamine / Q000737:chemistry; D004220:Disulfides; D006801:Humans; D007509:Irritants; D009092:Mucous Membrane; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000633:toxicity; D013552:Swine; D047391:alpha-Cyclodextrins / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000269:Adhesives; D004220:Disulfides; D007509:Irritants; D013438:Sulfhydryl Compounds; D047391:alpha-Cyclodextrins; D003543:Cysteamine; D017332:Cetirizine
keywords: Cetirizine (PubChem CID: 2678); Cyclohexaamylose (PubChem CID: 444913); Cysteamine (PubChem CID: 6058); Sodium cyanotrihydridoborate (PubChem CID: 20587905); Sodium metaperiodate (PubChem CID: 23667635); cetirizine; mucosal irritation; ocular mucosa; thiomers; α-cyclodextrin