Khar R K, Jain G K, Warsi M H, Mallick N, Akhter S, Pathan S A, Ahmad F J
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi - 110 062, India.
Indian J Pharm Sci. 2010 Nov;72(6):675-88. doi: 10.4103/0250-474X.84575.
Nucleic acid-based therapeutics have gained a lot of interest for the treatment of diverse ophthalmic pathologies. The first to enter in clinic has been an oligonucleotide, Vitravene(®) for the treatment of cytomegalovirus infection. More recently, research on aptamers for the treatment of age related macular degeneration has led to the development of Macugen(®). Despite intense potential, effective ocular delivery of nucleic acids is a major challenge since therapeutic targets for nucleic acid-based drugs are mainly located in the posterior eye segment, requiring repeated invasive administration. Of late, nanotechnology-based nano-vectors have been developed in order to overcome the drawbacks of viral and other non-viral vectors. The diversity of nano-vectors allows for ease of use, flexibility in application, low-cost of production, higher transfection efficiency and enhanced genomic safety. Using nano-vector strategies, nucleic acids can be delivered either encapsulated or complexed with cationic lipids, polymers or peptides forming sustained release systems, which can be tailored according to the ocular tissue being targeted. The present review focuses on developments and advances in various nano-vectors for the ocular delivery of nucleic acid-based therapeutics, the barriers that such delivery systems face and methods to overcome them.
基于核酸的疗法在治疗多种眼科疾病方面引起了广泛关注。首个进入临床的是一种寡核苷酸药物Vitravene（®），用于治疗巨细胞病毒感染。最近，针对年龄相关性黄斑变性的适配体研究促成了Macugen（®）的开发。尽管潜力巨大，但核酸的有效眼部递送仍是一项重大挑战，因为基于核酸的药物的治疗靶点主要位于眼后段，需要反复进行侵入性给药。近来，为克服病毒载体和其他非病毒载体的缺点，已开发出基于纳米技术的纳米载体。纳米载体的多样性使其易于使用、应用灵活、生产成本低、转染效率更高且基因组安全性增强。利用纳米载体策略，核酸可以通过包封或与阳离子脂质、聚合物或肽复合的方式递送，形成可持续释放系统，该系统可根据靶向的眼部组织进行定制。本综述重点关注用于眼部递送基于核酸的疗法的各种纳米载体的发展与进展、此类递送系统面临的障碍以及克服这些障碍的方法。
