In this work we focused on how the concentration of Labrasol® and preparation method of phospholipid vesicles might influence their physico-chemical features and skin delivery performances. Penetration Enhancer-containing Vesicles (PEVs) were prepared using caprylcaproyl macrogol-8 glyceride (Labrasol®, HLB 14), a solubilizer/penetration enhancer for topical formulations. A cheap and unpurified commercial mixture of phospholipids, fatty acids and triglycerides (Phospholipon® 50) was used to incorporate minoxidil (2% w/v). During the preparation, labrasol was added at different concentrations in the lipid phase or mixed with the water phase. The film hydration method was used, followed by sonication, when appropriate. The effects that these variables might have on PEVs colloidal characteristics were investigated. Multi- and oligolamellar vesicles were obtained, depending on the production procedure, around 100 nm, negatively charged (~ -60 mV), able to incorporate minoxidil in good yields (up to 74%), and stable during storage. Further, vesicles were evaluated for ex vivo (trans)dermal delivery through new born pig skin, showing improved minoxidil local accumulation, influenced by labrasol concentration and insertion in the aqueous or lipid phase of the vesicular formulations. Overall, it can be assumed that PEVs enhanced drug transport through the skin barrier thanks to a synergic effect of vesicles and labrasol. The proposed approach based on vesicular nanocarriers may hold promising therapeutic value for treating hair growth disorders, by increasing cutaneous minoxidil bioavailability and reducing transdermal permeation
