Formulation and Evaluation of SNEDDS Loaded with Original Lipophenol for the Oral Route to Prevent Dry AMD and Stragardt’s Disease

Abstract

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.

Overview of alkyl quercetin lipophenol synthesis and its protective effect against carbonyl stress involved in neurodegeneration

“…23–25 The importance of the alkyl (an isopropyl) and the omega-3 chain has been highlighted in cellular models. Such new lipophenolic derivatives were able to protect photoreceptor degeneration induced by light (80% of protection) in a murine model of genetic macular degeneration by IV and oral administration, 26,27 thus validating the proof of concept of the pre-clinical interest of those PUFA conjugates.…”

Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration

“…It alleviates DNA damage and methylglyoxal accumulation in the primary retinal pericytes of rats [310]. In another novel approach for managing dry AMD and Stargardt's disease, Vincent et al [311] reported photoreceptor protection by phloroglucinolisopropyl-DHA (IP-DHA), a lipophenol drug incorporated in a self-nanoemulsifying drug delivery system (SNEDDS) under acute and chronic light stress. It is irrefutably pivotal to highlight the rationale for the development of antioxidant formulations incorporating evidence-based antioxidants to effectively counteract the detrimental effect of oxidative damage.…”