• Flexible asymmetric liposomes were designed for transdermal DNA delivery. • The inner and outer lipid layers had different compositions • Inverse emulsion technique enabled efficient encapsulation of plasmid DNA. • Liposomes showed >80% cell viability and up to 35% transfection efficiency. • Findings highlight the potential of biocompatible nanocarriers for non-invasive gene delivery. As a versatile type of nanocarrier, liposomes have gained attention due to their biocompatibility, biodegradability, and ability to encapsulate a wide range of compounds. Asymmetric liposomes are characterized by distinct lipid compositions in their inner and outer layers, enhancing drug encapsulation and stability. Surfactant compounds and ethanol confer the flexibility of liposomes in their lipid layer. This characteristic allows liposomes to deform without breaking or releasing their contents, enabling them to cross complex barriers, such as the skin. This research investigates the innovative design and application of flexible asymmetric liposomes for transdermal DNA delivery. By using an adapted inverse emulsion technique, this study successfully encapsulated plasmid DNA within flexible asymmetric liposomes to evaluate its biocompatibility and skin permeation capacity in an in vitro model. Several formulations of liposomes containing DOTMA, DOPE, and/or cholesterol as the inner layer and DSPC, Span80, and/or ethanol as the outer layer were assessed through viability assay, transfection efficiency, and permeability testing using the Parallel Artificial Membrane Permeability Assay (PAMPA). All formulations demonstrated over 69% cell viability at a concentration of 5 μg, and transfection efficiency was significantly enhanced, reaching transfection rates of 32.37% ±3.32% in liposomes with all components. Permeability testing showed that the liposomal formulations exhibited high permeability, further improved by including ethanol and surfactants. Key findings indicate that cholesterol, Span 80, and ethanol substantially contribute to transfection rates and permeation. This research underscores the potential of flexible asymmetric liposomes for effective transdermal delivery of genetic material.
Gardea-Gutiérrez et al. (Wed,) studied this question.