Agban Yosra, Lian Jiaxin, Prabakar Sujay, Seyfoddin Ali, Rupenthal Ilva D
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.
Leather and Shoe Research Association of New Zealand, P.O. Box 8094, Palmerston North 4446, New Zealand.
Int J Pharm. 2016 Mar 30;501(1-2):96-101. doi: 10.1016/j.ijpharm.2016.01.069. Epub 2016 Jan 29.
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.
青光眼是一种常见的进行性眼部疾病，仍然是全球第二大致盲原因。目前的治疗方法包括频繁滴眼药水，这往往导致患者依从性差和治疗效果不佳。本研究的目的是通过开发一种新型的纳米颗粒交联胶原蛋白眼罩，用于持续递送盐酸毛果芸香碱（PHCl），以克服这些局限性。在选择ZnO/PVP纳米颗粒作为理想候选物之前，评估了三种金属氧化物纳米颗粒（NPs）；二氧化钛（TiO2）、氧化锌（ZnO）和聚乙烯吡咯烷酮（PVP）包覆的氧化锌（ZnO/PVP）的细胞毒性以及眼罩透明度。然后对交联胶原蛋白眼罩的机械强度、膨胀能力和生物粘附特性进行了表征，与普通薄膜相比，ZnO/PVP NP交联眼罩表现出最有利的特性。然后将具有最佳性能的眼罩负载PHCl，并在有无紫外线照射进一步交联的情况下测量锌离子以及PHCl的体外释放。释放的锌离子浓度远低于半数抑制浓度（IC50），使其在眼部使用时安全。此外，与ZnO/PVP NPs交联的胶原蛋白眼罩在14天内释放PHCl，为青光眼提供了一种有前景的缓释治疗选择。
