Mandal Abhirup, Bisht Rohit, Rupenthal Ilva D, Mitra Ashim K
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.
Buchanan Ocular Therapeutics Unit (BOTU), Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
J Control Release. 2017 Feb 28;248:96-116. doi: 10.1016/j.jconrel.2017.01.012. Epub 2017 Jan 11.
Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies.
由于存在多种消除机制和生理屏障，导致局部应用后眼部生物利用度较低，因此有效的眼内药物递送面临重大挑战。在过去几十年中，聚合物胶束已成为治疗影响眼前段（干眼综合征）和眼后段（年龄相关性黄斑变性、糖尿病视网膜病变和青光眼）眼部疾病最有前景的药物递送平台之一。来自体外和体内动物研究的有前景的临床前疗效结果已使其在临床试验中稳步推进。这些聚合物胶束的粘膜粘附特性导致与眼表的接触增强，而其小尺寸允许更好的组织渗透。最重要的是，由于这些聚合物胶束具有高度水溶性，它们可产生清澈的水溶液，这使得以滴眼液的形式易于应用，而不会产生任何视力干扰。聚合物胶束的其他优点包括稳定性增强、载药量更大、无毒副作用、易于表面修饰和可控药物释放。最后，简单且具有成本效益的制备技术使其在工业上的接受度相对较高。本综述总结了这些胶束作为眼用药物递送有效载体的结构框架、制备方法、物理化学性质、专利发明和最新进展，突出了它们在临床前研究中的性能。
