Stabilization of all-trans retinol by loading lipophilic antioxidants in solid lipid nanoparticles

Loading of drugs into the solid matrix of solid lipid nanoparticles (SLNs) can be one of effective means to protect them against chemical degradation. In this study, the SLNs for all-trans retinol (AR) were formulated to improve the stability of AR, whose chemical instability has been a limiting factor in its clinical use. First of all, the physicochemical properties of AR-loaded SLNs, including mean particle diameter and zeta potential, were modulated by changing the total amount of surfactant mixture and the mixing ratio of eggPC and Tween 80 as surfactant mixture. The AR-loaded SLNs formulation was irradiated with a 60-W bulb to investigate the photostability. The extent of photodegradation was measured by high-performance liquid chromatography. The mean particle diameter and zeta potential of the smallest SLNs were 96 nm and -28 mV, respectively. The loading of AR in optimized SLNs formulations rather decelerated the degradation of AR, compared with AR solution dissolved in methanol. Our subsequent study showed that the co-loading of antioxidants greatly enhanced the stability of AR loaded in SLNs, compared with those loaded in SLNs without antioxidant. The photostability at 12 h of AR in SLNs was enhanced folds (43% approximately) higher than that in methanol solution (about 11%). Furthermore, the protecting effect of antioxidants was greatly dependent on the type of antioxidant. Taken together, AR could be effectively stabilized by being loaded in SLNs together with an antioxidant BHT-BHA. (c) 2005 Elsevier B.V. All rights reserved.