Abstract
Transdermal skin delivery is a method to transport various topical formulations to a deeper skin layer non-invasively. Permeability analysis of many delivering agents has been mostly conducted by a simple tape stripping method. However, it cannot reveal a detailed depth-dependent distribution profile of transdermally delivered agents in the skin. In this work, we achieved a cellular-level depth-defined visualization of fluorophore-labelled human epidermal growth factor (EGF) transdermally delivered to human skin by using encapsulation with common liposomes and newly fabricated multi-lamellar nanostructures using a custom-design two-photon microscopy system. It was able to generate 3D reconstructed images displaying the distribution of human EGF inside the human skin sample with high-resolution. Based on a depthwise fluorescence intensity profile showing the permeation of human EGF, a quantitative analysis was performed to assess the transdermal delivery efficacy achieved by each formulation, showing a significant improvement of the efficacy with the utilization of multi-lamellar nanostructure.
Highlights
Skin is a barrier composed of three distinguishable layers: stratum corneum, epidermis and dermis, which protects the body from undesirable substances such as virus and bacteria [1, 2]
It was able to generate 3D reconstructed images displaying the distribution of human epidermal growth factor (EGF) inside the human skin sample with high-resolution
Based on a depthwise fluorescence intensity profile showing the permeation of human EGF, a quantitative analysis was performed to assess the transdermal delivery efficacy achieved by each formulation, showing a significant improvement of the efficacy with the utilization of multi-lamellar nanostructure
Summary
Skin is a barrier composed of three distinguishable layers: stratum corneum, epidermis and dermis, which protects the body from undesirable substances such as virus and bacteria [1, 2]. To establish the liposome as an effective carrier for transdermal delivery to deliver the functional agents to the targeted layer of the skin, encapsulation method to produce liposomes with high encapsulation efficiency and homogeneous size is critical [18,19,20]. Encapsulating efficacy of general liposome is quite low, typically about 10~20%, because of small volume ratio of the internal aqueous compartment [20, 21] To overcome this shortcoming, we newly fabricated a protein-lipid hybrid-type multi-lamellar nanostructured vesicle consists of a cationic lipid, 1,2-dioleoyl-3trimethylammonium-propane (DOTAP), which can potentially be an effective carrier to deliver functional agents such as human epidermal growth factor (EGF) into the dermal layer with high physiological activity. A quantitative analysis of three-dimensional distribution of transdermally delivered FITC-EGF in the skin layer were performed based on fluorescence signal of FITC, showing enhanced efficacy of transdermal delivery with DOTAP complex formulation
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