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

• Main Authors: Maxime Vincent (Author), Laurianne Simon (Author), Philippe Brabet (Author), Philippe Legrand (Author), Christophe Dorandeu (Author), Josephine Lai Kee Him (Author), Thierry Durand (Author), Céline Crauste (Author), Sylvie Begu (Author)
• Formato: Livro
• Publicado em: MDPI AG, 2022-05-01T00:00:00Z.
• Assuntos: article
• Acesso em linha: Connect to this object online.
• Notes: 10.3390/pharmaceutics14051029; 1999-4923
• Keywords: dry age-related macular degeneration (AMD); Stargardt's disease (STGD1); self-nanoemulsifying drug delivery system (SNEDDS); antioxidant; lipophenol; oral delivery; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 5, p 1029 (2022)

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 (<i>w</i>/<i>w</i>/<i>w</i>), 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.