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

Maxime Vincent (1) , Laurianne Simon (1) , Philippe Brabet (2) , Philippe Legrand (1) , Christophe Dorandeu (1) , Josephine Lai Kee Him (3) , Thierry Durand (4) , Céline Crauste (4) , Sylvie Begu (1)

1 ICGM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier
2 INM - Institut des Neurosciences de Montpellier
3 CBS - Centre de Biologie Structurale [Montpellier]
4 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

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.

Mots clés: Stargardt’s disease (STGD1); antioxidant; dry age-related macular degeneration (AMD); lipophenol; oral delivery; self-nanoemulsifying drug delivery system (SNEDDS)

Domaines: Sciences du Vivant [q-bio]

Maxime Vincent, Laurianne Simon, Philippe Brabet, Philippe Legrand, Christophe Dorandeu, et al.. Formulation and Evaluation of SNEDDS Loaded with Original Lipophenol for the Oral Route to Prevent Dry AMD and Stragardt’s Disease. Pharmaceutics, 2022, 14 (5), pp.1029. ⟨10.3390/pharmaceutics14051029⟩. ⟨hal-03681400⟩