A novel lipophenol quercetin derivative to prevent macular degeneration: Intravenous and oral formulations for preclinical pharmacological evaluation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue International Journal of Pharmaceutics Année : 2024

A novel lipophenol quercetin derivative to prevent macular degeneration: Intravenous and oral formulations for preclinical pharmacological evaluation

Philippe Brabet
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Résumé

Drugs with properties against oxidative and carbonyl stresses are potential candidates to prevent dry age-related macular degeneration (Dry-AMD) and inherited Stargardt disease (STGD1). Previous studies have demonstrated the capacity of a new lipophenol drug: 3-O-DHA-7-O-isopropyl-quercetin (Q-IP-DHA) to protect ARPE19 and primary rat RPE cells respectively from A2E toxicity and under oxidative and carbonyl stress conditions. In this study, first, a new methodology has been developed to access gram scale of Q-IP-DHA. After classification of the lipophenol as BCS Class IV according to physico-chemical and biopharmaceutical properties, an intravenous formulation with micelles (M) and an oral formulation using lipid nanocapsules (LNC) were developed. M were formed with Kolliphor® HS 15 and saline solution 0.9 % (mean size of 16 nm, drug loading of 95 %). The oral formulation was optimized and successfully allowed the formation of LNC (25 nm, 96 %). The evaluation of the therapeutic potency of Q-IP-DHA was performed after IV administration of micelles loaded with Q-IP-DHA (M-Q-IP-DHA) at 30 mg/kg and after oral administration of LNC loaded with Q-IP-DHA (LNC-Q-IP-DHA) at 100 mg/kg in mice. Results demonstrated photoreceptor protection after induction of retinal degeneration by acute light stress making Q-IP-DHA a promising preventive candidate against dry-AMD and STGD1.
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Dates et versions

hal-04386862 , version 1 (11-01-2024)

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Maxime Vincent, Jordan Lehoux, Claire Desmarty, Esperance Moine, Philippe Legrand, et al.. A novel lipophenol quercetin derivative to prevent macular degeneration: Intravenous and oral formulations for preclinical pharmacological evaluation. International Journal of Pharmaceutics, 2024, 651, pp.123740. ⟨10.1016/j.ijpharm.2023.123740⟩. ⟨hal-04386862⟩
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