Abstract:
Glaucoma is a neurodegenerative condition that results in the damage of retinal ganglion cells due to elevated intraocular pressure (IOP). To curtail the limitations associated with conventional treatments such as eye drops and ocular suspensions, we have developed \'single\' and \'dual\' drug delivery contact lenses (CLs), that is, latanoprost (LP) and latanoprost-timolol (LP-TM) deliverable CLs, in response to lysozyme (Lyz), which is abundant in the lacrimal fluid. Since chitosan (CS) can entrap more of the drug and also undergo hydrolysis in the presence of Lyz, we have employed CS for the composite preparation. The CL fabrication was performed by free radical copolymerization of poly(2-hydroxyethyl methacrylate) (pHEMA) in the presence of the drug-loaded nanocomposite with UV-curing initiators using the pre-drug loading strategy. The surface morphological, optical and mechanical investigations confirmed the presence of the drugs, ≥80% transparency, the adequate flexibility and biocompatibility of both the CLs. The in vitro release experiments showed the release of 95.86% LP from LP-CL, and 83.87% LP and 86.70% TM from LP-TM-CL in the presence of 1.5 mg mL-1 of Lyz in 72 h. In vitro biocompatibility assay against human corneal epithelial (HCE) cells and ex vivo experiments on HET-CAM confirmed that the fabricated LP-CL and LP-TM-CL are well tolerated. Moreover, in vivo safety evaluations of CLs on New Zealand white rabbit eyes suggest no sign of irritation to the ocular tissues within 72 h of observation. Hence, the study suggests that the \'single\' and \'dual\' drug-loaded CLs could open a new avenue to manage glaucoma by maintaining mean diurnal IOP.
摘要:
青光眼是一种神经退行性疾病,由于眼内压(IOP)升高而导致视网膜神经节细胞受损。为了减少与常规治疗相关的局限性,如滴眼液和眼部悬浮液,我们开发了“单”和“双”给药隐形眼镜(CLs),也就是说,拉坦前列素(LP)和拉坦前列素-噻吗洛尔(LP-TM)可交付CLs,响应溶菌酶(Lyz),它在泪液中很丰富。由于壳聚糖(CS)可以捕获更多的药物,并且在Lyz的存在下也会发生水解,我们采用CS制备复合材料。CL的制造是通过聚(甲基丙烯酸2-羟乙酯)(pHEMA)的自由基共聚在药物负载的纳米复合材料与UV固化引发剂的存在下使用预药物负载策略进行的。表面形态,光学和机械研究证实了药物的存在,透明度≥80%,两种CLs具有足够的灵活性和生物相容性。体外释放实验表明,从LP-CL中释放95.86%的LP,在72小时内存在1.5mgmL-1的Lyz的情况下,来自LP-TM-CL的LP和83.87%的TM。针对人角膜上皮(HCE)细胞的体外生物相容性测定和HET-CAM的离体实验证实,制造的LP-CL和LP-TM-CL具有良好的耐受性。此外,CLs对新西兰白兔眼的体内安全性评估表明,在观察后72小时内没有对眼组织的刺激迹象。因此,该研究表明,'单'和'双'载药CLs可以通过维持平均昼夜IOP来治疗青光眼开辟一条新途径.