Invasomes have been widely exploited to enhance the percutaneous permeation of drugs. On the other hand, few studies have been dedicated to evaluating how their composition impacts the interaction with the skin, vesicle rigidity and stability, which was the focus of this investigation. Light scattering and spectroscopic techniques were considered for vesicle characterization. The addition of cholesterol (CHOL) into the phosphatidylcholine (PC) vesicles led to increased membrane rigidity (from PC:CHOL 5:0.5) and a concentration-dependent disorder effect on skin domains. Nevertheless, these vesicles were showed to be less stable. Ethanol, in turn, resulted in larger and more flexible vesicles, which can be attributed to its preferential distribution in headgroups of PC. The effect of limonene on membrane rigidity was dependent on the vesicle composition. It reduced the rigidity when few constituents were considered, but an opposite effect was observed for vesicles containing PC, CHOL, ethanol and limonene. Competitive effects of limonene and CHOL by the same domains in PC could explain these findings. Limonene was crucial to obtaining more monodisperse vesicles and it showed a synergistic action with CHOL in the disruption of lipid domains in the skin. Invasomes were more stable than liposomes. CHOL-free invasomes showed to be stable for up to 40 days at room temperature.
Keywords: Invasomes; Limonene; Rigidity; Skin interaction; Stability.
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