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人工晶状体作为药物输送装置。

Intraocular lenses as drug delivery devices.

机构信息

CQE, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.

CQE, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.

出版信息

Int J Pharm. 2021 Jun 1;602:120613. doi: 10.1016/j.ijpharm.2021.120613. Epub 2021 Apr 16.

Abstract

Cataract surgery is one of the most common and safe surgical procedures nowadays. However, it is not free of risks as endophthalmitis, ocular inflammation and posterior capsule opacification (PCO) can appear as post-surgery complications. The usual eye drop therapy used as prophylaxis for the former two complications has limited bioavailability. In turn, the prevention of PCO involves an adequate surgical technique and a careful choice of intraocular lens (IOL) design and material. Also, different drugs have been tested to reduce incidence of PCO, but no prophylaxis demonstrated to be completely effective. In the past few years, IOLs have been proposed as drug delivery devices to replace or/assist the usual eye drop therapy in the post-operatory period. The great advantage of drug loaded IOLs would be to ensure a continuous drug delivery, independent of patient's compliance without requiring any further action besides IOL implantation. The biggest challenge of drug loaded IOLs production is to achieve a controlled and extended release that meet therapeutic needs without inducing toxicity to the surrounding ocular tissues or affecting the physical properties of the lens. This review starts by addressing the possible complications after cataract surgery, as well as the most commonly adopted prophylaxis for each of them. The various types of IOLs are described and their main advantages/disadvantages are discussed. The different strategies pursued to incorporate drugs into the IOLs and control their release, which include soaking the IOL in the drugs solution, supercritical impregnation, surface modifications, and attachment of drug reservoirs to the IOL, among others, are reported. For each strategy, a summary of the publications is presented, which includes the target complication, the types and amounts of released drugs and the IOL materials. A brief description of each individual study is given afterwards. Optimization of drug loaded IOLs through mathematical modelling and possible issues raised by their sterilization are also tackled. At the end, the future commercialization of drug loaded IOLs is commented.

摘要

白内障手术是当今最常见和安全的手术之一。然而,它并非没有风险,因为术后可能会出现眼内炎、眼内炎症和后囊混浊(PCO)等并发症。通常用于预防前两种并发症的眼药水治疗方法生物利用度有限。反过来,预防 PCO 涉及到适当的手术技术和仔细选择人工晶状体(IOL)的设计和材料。此外,已经测试了不同的药物来降低 PCO 的发生率,但没有一种预防方法被证明是完全有效的。在过去的几年中,已经提出了将 IOL 用作药物输送装置,以替代或/辅助术后常规滴眼治疗。载药 IOL 的最大优势将是确保持续的药物输送,独立于患者的依从性,而无需在植入 IOL 之外进行任何进一步的操作。载药 IOL 生产的最大挑战是实现受控和延长释放,以满足治疗需求,而不会对周围眼组织产生毒性或影响晶状体的物理性质。本综述首先介绍了白内障手术后可能出现的并发症,以及针对每种并发症最常采用的预防措施。描述了各种类型的 IOL,并讨论了它们的主要优缺点。报告了将药物纳入 IOL 并控制其释放的不同策略,包括将 IOL 浸泡在药物溶液中、超临界浸渍、表面改性以及将药物储库附着到 IOL 等。对于每种策略,都介绍了出版物的摘要,其中包括目标并发症、释放的药物类型和数量以及 IOL 材料。随后简要描述了每个单独的研究。还讨论了通过数学建模对载药 IOL 进行优化以及它们的灭菌可能引发的问题。最后,对载药 IOL 的未来商业化进行了评论。

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