Abstract

In current clinical settings, frequent intravitreal (IVT) injections of anti-vascular endothelial growth factors are used due to their short in-vivo half-life and rapid clearance from the back of the eye. The IVT injections are associated with pain, risk of infection, retinal detachment, and financial burden. Biologics molecules can undergo physical, chemical, and enzymatic degradation during formulation development and in the biological environment. Moreover, the complex ocular structures also act as a rate-limiting barrier for these biologics. Thus, delivering stable and clinically relevant biologics concentration to the back of the eye is still a challenge. Compare to other drug delivery platforms, injectable in-situ gelling depot systems (IISGDs) have emerged as an effective system for biologics delivery. In this review, we have discussed various biologics used in ocular therapeutics and their associated challenges. Different routes of delivery and associated tissue barriers are also discussed. Different types of IISGDs developed to date for biologics delivery to the back of the eye were also covered. To conclude, various critical parameters related to the formulation development process and injectable depot systems that need careful consideration and further investigations were highlighted.

摘要

在目前的临床环境中，经常使用玻璃体内 (IVT) 注射抗血管内皮生长因子，因为它们的体内半衰期短且能从眼后部快速清除。IVT 注射与疼痛、感染风险、视网膜脱离和经济负担有关。生物制剂分子可以在制剂开发过程中和在生物环境中经历物理、化学和酶促降解。此外，复杂的眼部结构也是这些生物制剂的限速屏障。因此，将稳定且临床相关的生物制剂浓度输送到眼后仍然是一个挑战。与其他药物输送平台相比，可注射原位凝胶储存系统 (IISGD) 已成为一种有效的生物制剂输送系统。在这次审查中，我们已经讨论了用于眼部治疗的各种生物制剂及其相关挑战。还讨论了不同的递送途径和相关的组织屏障。迄今为止开发的用于将生物制剂输送到眼后的不同类型的 IISGD 也包括在内。总而言之，强调了需要仔细考虑和进一步调查的与制剂开发过程和注射储存系统相关的各种关键参数。