Chemical stability and in vitro and clinical efficacy of a novel hybrid retinoid derivative, bis-retinamido methylpentane

Abstract

The anti-aging agent, retinol, has fewer side effects and similar biological activity compared to retinoic acid. However, retinol becomes unstable when exposed to light and heat. A novel hybrid retinoid derivative, bis-retinamido methylpentane (RS-2A), was newly developed to overcome the limitations. This study evaluated the chemical stability of RS-2A under thermal and light conditions by examining degradation profiles, and assessed the in vitro biological activity, cytotoxicity, and clinical efficacy. Chemical stability and degradation profiles were investigated with HPLC and LC-MS. Especially, photostability of RS-2A was analyzed under various conditions, such as change of physical state and concentration, different solvents, and various excipients. For analyses of cellular activity and cytotoxicity, human dermal fibroblasts were cultured with RS-2A. To evaluate the safety and efficacy of the compound with the cellular results, RS-2A was applied to women who had moderate to severe wrinkles at the periorbital region. All of the experiments were conducted with retinol as a reference. RS-2A was more stable than retinol to thermal conditions, especially in solution. Both RS-2A and retinol were unstable to light, but RS-2A showed enhanced photo-stability with regard to concentration, more polar solvent, and addition of proper excipients. RS-2A exhibited decreased cytotoxicity and enhanced effects on collagen synthesis compared with retinol. In a clinical study, a 4-week treatment with RS-2A significantly improved the appearance of periorbital wrinkles without any side effects. The results indicate that RS-2A might have potential as an anti-aging agent for cosmeceutical preparations because of its enhanced chemical stability, biological activity, safety, and clinical efficacy. (C) 2015 Elsevier B.V. All rights reserved.