Novel small self-assembled resveratrol-bearing cubosomes and hexosomes: preparation, charachterization, and ex vivo permeation.

The study aims to elaborate novel self-assembled liquid crystalline nanoparticles (LCNPs) of resveratrol which has neuro-protective, anti-aging, and anticancer activity. Resveratrol loaded LCNPs fabrication and optimization for transdermal delivery was assessed via a quality by design approach based on 2 full factorial designs. The cubic phase of LCNPs was successfully prepared using GMO (glyceryl monooleate) via the emulsification technique. Based on the factorial design, the independent operating variables significantly affected the five dependent responses. The cubosomes and hexosomes hydrodynamic diameters were in the nanometer range (135-256 nm) with narrow particle size distribution, high negative zeta potential ≥ -27.9 mV, and entrapment efficiency ≥73.5%. The LCNPs succeeded in sustaining resveratrol release for almost 24 h, following a non-fickian transport of drug diffusion mechanism. Ex-vivo study revealed a significant enhancement up to six folds in the transdermal permeation of resveratrol-loaded LCNPs compared to its suspension. The selected LCNPs exhibited a high physical stability while retaining the cubic structure for at least 3 months. Quality by design approach successfully accomplished a predictable mathematical model permitting the development of novel LCNPs for sustained transdermal delivery of resveratrol.