Nanoemulgel formulation for topical delivery of plant glucosylceramide: Characterization and optimization

Abstract

Plant sphingolipids (SPLs) are available as oral or topical skin care products in order to restore skin protective nature due to their chemical similarity with human skin ceramides (CERs). However, successful delivery of glucosylceramide (GlcCER) to the viable epidermis is challenging due to the skin barrier nature. The current study aimed to develop and characterize optimized nanoemulsion (NE) and nanoemulgel (NEG) formulations for topical delivery of lupin GlcCERs. The NE components were screened and pseudo-ternary phase diagrams were constructed at different hydrophilic-lipophilic balance (HLB) values of surfactant-co-surfactant mixture (Smix). Extreme vertices mixture design was developed to investigate the impact of percentage compositions of the independent variables; oil mixture (2–3%), Smix (15–18%) and aqueous component (79–83%) on the globule size of the NEs. Then, NEG was prepared from optimized 0.25% lupin GlcCER NE and Carbopol 980 gel. HLB values of 13.5 and 12 provided broader NE regions for Miglyol and isopropyl myristate, respectively. The analysis of variance of the quadratic model showed suitability of the model with R2 of 99.80 and non-significant lack of fit (F value = 17.06). The optimized percentage compositions of oil phase, Smix and aqueous phase were 2.15%, 16.39% and 81.46%, respectively, with predicted globule size of 23.96 nm. Accordingly, the optimized NE globule size, poly dispersity index and zeta potential were 23.93 ± 0.25 nm, 0.069 ± 0.017 and 23.95 ± 1.20 mV, respectively. The oil globules were spherical and distributed uniformly without aggregation. The NE exhibited Newtonian flow with a viscosity of 6.75 mPa s while NEGs showed non-Newtonian flow with shear thinning property. The amount of lupin GlcCER released and penetrated into each model membrane layer at different time point was in the order of NEs > basic cream > NEGs. After 180 min, 51%, 84% and 96% of lupin GlcCER was released and penetrated into the model membrane layers from NEG, basic cream and NEs, respectively. NEGs prolonged the release and slowed down the penetration of GlcCER into the multilayer membrane model which is crucial to limit its penetration into the epidermal skin layer. Therefore, NEGs could be considered as an option for the delivery of plant GlcCER into the upper part of the skin after further ex-vivo investigation as the study is the first of its kind.