Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil

Abstract Donepezil is one of the main compounds used in the therapy of Alzheimer’s disease. Oral administration of this drug presents many drawbacks, resulting in treatment non-adherence among patients. Thus, the development of transdermal formulations for donepezil delivery is important. The aim of this study was to prepare and to evaluate nanostructured lipid carrier-based gels (NLC gel) able to improve the skin delivery of donepezil free base (DPB). The components of nanostructured lipid carriers (NLCs) were selected after evaluating their enhancing effects using in vitro DPB skin delivery assays. DPB-loaded NLC were prepared by a microemulsion technique, by employing stearic acid as a solid lipid, oleic acid as a liquid lipid, lecithin as a surfactant, and sodium taurodeoxycholate as a co-surfactant. The DPB-NLC dispersions were characterized morphologically using atomic force microscopy and physicochemically using dynamic light scattering and surface charge measurements. These data along, with the encapsulation studies, indicated that uniformly nano-sized particles with high drug encapsulation were fabricated. In vitro skin permeation assays were performed, and the results indicated that drug skin permeation from DPB-NLC gel was increased, not only by the enhancing effect of their components, but the lipid nanocarriers also presented an additional enhancing effect to increase drug flux across the skin. Therefore, DPB-NLC gel is an interesting formulation for the enhanced treatment of Alzheimer’s disease.