a Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Faculty of Medical and Health Sciences , University of Auckland , Auckland , New Zealand.
b Auckland Cancer Society Research Center, Faculty of Medical and Health Sciences , University of Auckland , Auckland , New Zealand.
Expert Opin Drug Deliv. 2016 Jul;13(7):953-62. doi: 10.1517/17425247.2016.1163334. Epub 2016 Mar 24.
Frequent intravitreal injections are currently the preferred treatment method for diseases affecting the posterior segment of the eye. However, these repeated injections have been associated with pain, risk of infection, hemorrhages, retinal detachment and high treatment costs. To overcome these limitations, light-responsive in situ forming injectable implants (ISFIs) may emerge as novel systems providing site-specific controlled drug delivery to the retinal tissues with great accuracy, safety, minimal invasiveness and high cost efficiency.
Complex ocular barriers, routes for drug delivery, types of injectable implants, ocular application of light and benefits of light-responsive systems are discussed with regards to challenges and strategies employed for effective drug delivery to the posterior segment of the eye. In particular, we have highlighted photoresponsive moieties, photopolymerization mechanisms and different development strategies with their limitations as well as recent advancements in the field.
Biodegradable light-responsive ISFIs are promising drug delivery systems that have shown a high degree of biocompatibility with sustained drug release in a number of applications. However, their use in intravitreal drug delivery is still in the very early stages. Issues related to the biocompatibility of the photoinitiator and the elimination of photo-degraded by-products from the ocular tissues need careful consideration, not only from a chemistry standpoint, but also from a biological perspective to improve the suitability of these systems for clinical applications.
目前,频繁的玻璃体内注射是治疗影响眼后段疾病的首选方法。然而,这些反复的注射会引起疼痛、感染风险、出血、视网膜脱离和高昂的治疗费用。为了克服这些限制,光响应原位形成可注射植入物(ISFI)可能成为提供对视网膜组织进行精确、安全、微创和高效成本效益的局部控制药物递送的新型系统。
本文讨论了复杂的眼部屏障、药物递送途径、可注射植入物的类型、眼部的光应用以及光响应系统的优势,以及为将药物有效递送至眼后段而采用的挑战和策略。特别是,我们强调了光响应部分、光聚合机制和不同的开发策略及其局限性,以及该领域的最新进展。
可生物降解的光响应 ISFI 是很有前途的药物递送系统,在许多应用中表现出高度的生物相容性和持续的药物释放。然而,它们在玻璃体内药物递送中的应用仍处于早期阶段。与光引发剂的生物相容性以及从眼部组织中消除光降解副产物相关的问题需要仔细考虑,不仅从化学角度,而且从生物学角度,以提高这些系统用于临床应用的适宜性。