title: Nanoparticle cross-linked collagen shields for sustained delivery of pilocarpine hydrochloride.
abstract: Glaucoma is a common progressive eye disorder which remains the second leading cause of blindness worldwide. Current therapy involves frequent administration of eye drops which often results in poor patient adherence and therapeutic outcomes. The aim of this study was to overcome these limitations by developing a novel nanoparticle cross-linked collagen shield for sustained delivery of pilocarpine hydrochloride (PHCl). Three metal oxide nanoparticles (NPs); titanium dioxide (TiO2), zinc oxide (ZnO) and polyvinylpyrrolidone (PVP) capped zinc oxide (ZnO/PVP), were evaluated for their cytotoxicity as well as shield transparency before selecting ZnO/PVP NPs as the ideal candidate. Cross-linked collagen shields were then characterized for their mechanical strength, swelling capacity and bioadhesive properties, with ZnO/PVP NP cross-linked shields showing the most favorable characteristics compared to plain films. The shield with the best properties was then loaded with PHCl and in vitro release of zinc ions as well as PHCl was measured without and with further cross-linking by ultraviolet irradiation. The concentration of zinc ions released was well below the IC50 rendering them safe for ocular use. Moreover, collagen shields cross-linked with ZnO/PVP NPs released PHCl over a period of 14 days offering a promising sustained release treatment option for glaucoma.
authors.affiliation: Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand; School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Agban
authors.affiliation: Leather and Shoe Research Association of New Zealand, P.O. Box 8094, Palmerston North 4446, New Zealand.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Lian
authors.affiliation: Leather and Shoe Research Association of New Zealand, P.O. Box 8094, Palmerston North 4446, New Zealand.
authors.forename: Sujay
authors.initials: S
authors.lastname: Prabakar
authors.affiliation: School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Ali
authors.initials: A
authors.lastname: Seyfoddin
authors.affiliation: Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. Electronic address: i.rupenthal@auckland.ac.nz.
authors.forename: Ilva D
authors.initials: ID
authors.lastname: Rupenthal
mesh_terms: D000268:Adhesiveness; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000008:administration & dosage* / Q000737:chemistry; D003315:Cornea / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008916:Miotics / Q000008:administration & dosage / Q000737:chemistry; D010862:Pilocarpine / Q000008:administration & dosage* / Q000737:chemistry; D011205:Povidone / Q000008:administration & dosage* / Q000737:chemistry; D014025:Titanium / Q000008:administration & dosage* / Q000737:chemistry; D015034:Zinc Oxide / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D008916:Miotics; D010862:Pilocarpine; C009495:titanium dioxide; D003094:Collagen; D014025:Titanium; D011205:Povidone; D015034:Zinc Oxide
keywords: Collagen shields; Cross-linking; Metal oxides; Nanoparticles; Ocular drug delivery