Dry age-related macular degeneration (Dry AMD) and Stargardt’s disease (STGD1) are common eye diseases, characterized by oxidative and carbonyl stress (COS)-inducing photoreceptor degeneration and vision loss. Previous studies have demonstrated the protective effect of photoreceptors after the intravenous administration of a new lipophenol drug, phloroglucinol-isopropyl-DHA (IP-DHA). In this study, we developed an oral formulation of IP-DHA (BCS Class IV) relying on a self-nanoemulsifying drug delivery system (SNEDDS). SNEDDS, composed of Phosal^® 53 MCT, Labrasol^®, and Transcutol HP^® at a ratio of 25/60/15 (w/w/w), led to a homogeneous nanoemulsion (NE) with a mean size of 53.5 ± 4.5 nm. The loading of IP-DHA in SNEDDS (SNEDDS-IP-DHA) was successful, with a percentage of IP-DHA of 99.7% in nanoemulsions. The in vivo study of the therapeutic potency of SNEDDS-IP-DHA after oral administration on mice demonstrated photoreceptor protection after the induction of retinal degeneration with acute light stress (73–80%) or chronic light stress (52–69%). Thus, SNEDDS formulation proved to increase the solubility of IP-DHA, improving its stability in intestinal media and allowing its passage through the intestinal barrier after oral force-fed administration, while maintaining its biological activity. Therefore, SNEDDS-IP-DHA is a promising future preventive treatment for dry AMD and STGD1.

中文翻译：

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用于口服途径预防干性 AMD 和 Stragardt 病的 SNEDDS 的配方和评价

干性年龄相关性黄斑变性 (Dry AMD) 和 Stargardt 病 (STGD1) 是常见的眼部疾病，其特征是氧化和羰基应激 (COS) 诱导的光感受器变性和视力丧失。以前的研究已经证明了在静脉内给予一种新的脂酚药物间苯三酚-异丙基-DHA (IP-DHA) 后光感受器的保护作用。在这项研究中，我们开发了一种依赖自纳米乳化给药系统 (SNEDDS) 的 IP-DHA (BCS IV 类) 口服制剂。SNEDDS，由 Phosal ^® 53 MCT、Labrasol和 Transcutol HP ^®组成，比例为 25/60/15 ⁽ w / w / w)，产生平均尺寸为 53.5 ± 4.5 nm 的均质纳米乳液 (NE)。IP-DHA 在 SNEDDS (SNEDDS-IP-DHA) 中的加载是成功的，在纳米乳液中 IP-DHA 的百分比为 99.7%。对小鼠口服 SNEDDS-IP-DHA 治疗效力的体内研究表明，在急性光应激 (73-80%) 或慢性光应激 (52-69%) 诱导视网膜变性后，光感受器具有保护作用。因此，SNEDDS 配方被证明可以增加 IP-DHA 的溶解度，提高其在肠道介质中的稳定性，并在口服强制喂食后允许其通过肠道屏障，同时保持其生物活性。因此，SNEDDS-IP-DHA 是一种很有前途的未来干性 AMD 和 STGD1 的预防性治疗方法。