Exploration of Microneedle-assisted skin delivery of cyanocobalamin formulated in ultraflexible lipid vesicles

Abstract

Vitamin B12 (cyanocobalamin) deficiency is a widespread condition because of its different aetiologies, like malabsorption syndrome or lifestyles as strict veganism that is increasing its incidence and prevalence in developed countries. It has important haematological consequences that require pharmacological treatment. Current therapy consists of oral or parenteral supplements of cyanocobalamin; however, the oral route is discarded for malabsorption syndrome patients and the parenteral route is not well accepted generally. Topical treatments have been suggested as an alternative, but the molecular weight and hydrophilicity of cyanocobalamin limits its diffusion through the skin. Lipid vesicles can allow the transdermal absorption of molecules > 500 Da. The aim of this work was to use different ultraflexible lipid vesicles (transfersomes and ethosomes) to enhance cyanocobalamin transdermal delivery. Vesicles were characterized and lyophilised for long-term stability. The ability to deliver cyanocobalamin through the skin was assessed in vitro using full-thickness porcine skin in Franz diffusion cells. As expected, the best transdermal fluxes were provided by ultraflexible vesicles, in comparison to a drug solution. Moreover, the pre-treatment of the skin with a solid microneedle array boosts the amount of drug that could potentially reach the systemic circulation.