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聚合物纳米粒子载普罗布考和石胆酸:氧化应激诱导的视网膜病变的一种新的治疗方法。

Polymer-Based Nanoparticles with Probucol and Lithocholic Acid: A Novel Therapeutic Approach for Oxidative Stress-Induced Retinopathies.

机构信息

The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, Western Australia 6102, Australia.

Centre for Ophthalmology and Visual Science (Incorporating the Lions Eye Institute), The University of Western Australia, Perth, Western Australia 6009, Australia.

出版信息

Mol Pharm. 2024 Jul 1;21(7):3566-3576. doi: 10.1021/acs.molpharmaceut.4c00269. Epub 2024 Jun 20.

Abstract

Oxidative stress is pivotal in retinal disease progression, causing dysfunction in various retinal components. An effective antioxidant, such as probucol (PB), is vital to counteract oxidative stress and emerges as a potential candidate for treating retinal degeneration. However, the challenges associated with delivering lipophilic drugs such as PB to the posterior segment of the eye, specifically targeting photoreceptor cells, necessitate innovative solutions. This study uses formulation-based spray dry encapsulation technology to develop polymer-based PB-lithocholic acid (LCA) nanoparticles and assesses their efficacy in the 661W photoreceptor-like cell line. Incorporating LCA enhances nanoparticles' biological efficacy without compromising PB stability. studies demonstrate that PB-LCA nanoparticles prevent reactive oxygen species (ROS)-induced oxidative stress by improving cellular viability through the nuclear erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. These findings propose PB-LCA nanoparticles as a promising therapeutic strategy for oxidative stress-induced retinopathies.

摘要

氧化应激在视网膜疾病的进展中起着关键作用,导致各种视网膜成分的功能障碍。一种有效的抗氧化剂,如普罗布考(PB),对于对抗氧化应激至关重要,并且作为治疗视网膜变性的潜在候选药物出现。然而,将亲脂性药物(如 PB)递送到眼睛的后段,特别是靶向光感受器细胞,存在挑战,需要创新的解决方案。本研究使用基于配方的喷雾干燥包封技术来开发基于聚合物的 PB-石胆酸(LCA)纳米粒子,并评估其在 661W 光感受器样细胞系中的功效。LCA 的掺入增强了纳米粒子的生物学功效,而不影响 PB 的稳定性。研究表明,PB-LCA 纳米粒子通过核红细胞 2 相关因子 2(Nrf2)/血红素加氧酶-1(HO-1)途径提高细胞活力,预防活性氧(ROS)诱导的氧化应激。这些发现提出 PB-LCA 纳米粒子作为治疗氧化应激诱导的视网膜病变的有前途的治疗策略。

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