Preparation And Skin Permeation Study Of Idebenone Loaded Nanostructured Lipid Carriers

Idebenone (IDB) is a powerful antioxidant and analogue of coenzyme Q10. Toimprove the chemical stability and the skin delivery of IDB, nanostructured lipidcarriers (NLC) was selected as IDB delivery system for topical use.1. Modified high shear and ultrasound method was selected to produceIDB-loaded NLC, the optimal technique was determined by single-factor selectingexperiment. The optimal prescription was that: concentration of Tween80andSoybean phosphatidylcholine (SPC)(surfacantes) was5.0%(Tween/SPC：8:1);concentration of Glyceryl palmito-stearate (solid lipid)，medium chain fatty acidtriglycerides (liquid lipid) and IDB was7.0%,3.0%and0.5%, respectively. Theoptimized IDB-loaded NLC was89.8nm, zeta potential was-29.6mV, encapsulationefficiency (EE) was99.4%, and release in constant manner during72h.2. The physical stability of different formulations (IDB-loaded NLC, NE and oilsolution) and in which chemical stability of IDB was determined during storage. Thechanges of particle size, zeta potential and EE of IDB-loaded NLC and NE weredetected during180days, results showed that the physical stability of NLC was muchbetter than NE;25℃and preserved in dark place was the best storage condition forNLC. Samples of the three formulations were placed at40℃, a relative humidity of75%and intensity of illumination3000lx condition for180days, the residualpercentage of IDB loaded in NLC, NE and in oil solution was90.1%,65.4%and51.3%, respectively.3. The penetration ability of the three formulations was tested ex vivo and in vivousing guinea pig skin as the model membrane. Ex vivo permeation experimentsrevealed that the cumulative amount of IDB in the epidermis, dermis and acceptormedium of NLC was approximately3-fold more than NE or oil solution at the end of24-hour experiment. No significant difference between NE and oil solution wasobserved in the enhancement of penetration efficacy of IDB. IDB amount in bloodand IDB cumulative amount in the skin were separately detected during and after6hof in vivo permeation experiments. IDB amount in blood were low for all threeformulations, but IDB amount of NLC formulation was comparably higher then NEand oil solution formulations, suggesting a better skin permeation ability of NLC. The permeability coefficient (Kp) and the enhancement ratio (ER) were calculated fromthe detected cumulative amount of IDB in skin, results showed that ER of NLC wasabout4-fold of conventional NE and oil solution formulations.The results obtained here demonstrated that the abilities of NLC to improve thechemical stability of IDB and enhance the skin permeation are much better than NEand oil solution. These suggest that IDB-loaded NLC have significant potential usefor skin care as an alternative topical formulation.