Keratin-Functionalized Transfersomes for Improving the Skin Permeation and Deposition of Podophyllotoxin

Podophyllotoxin (POD) serves as the primary therapeutic agent for the external management of genital warts. However, traditional POD tinctures often cause severe systemic adverse reactions, due to the drug being absorbed through the skin into the bloodstream. Therefore, it is particularly important to develop new topical preparations for POD to enhance topical administration and reduce systemic absorption. Herein, POD-loaded keratin-functionalized transfersomes (POD-KTFs) were developed and characterized, and the skin permeation and deposition, the intradermal fluorescence distribution, and the influence of POD-KTFs on a skin structure were evaluated. The hydrodynamic diameter and surface potential of POD-KTFs were 183.1 nm and -33.9 mV, respectively. The image of scanning electron microscopy (SEM) indicated that the POD-KTFs had a spherical appearance. The X-ray diffraction (XRD) pattern confirmed that POD mainly existed in its amorphous form in POD-KTFs. Meaningfully, POD-KTFs increased the deposition of POD in porcine ear skin by 2.14 and 1.80 times, respectively, compared to the POD tincture and POD-loaded transfersomes (POD-TFs), while the transdermal penetration of POD in POD-KTFs was obviously less than that of POD tincture (p < 0.001) and POD-TFs (p < 0.01). Using coumarin-6 as a fluorescent probe, fluorescence imaging of skin sections revealed that the POD-KTFs were mainly distributed in the epidermis. In addition, POD-TFs could promote the drug to pass through the stratum corneum (SC) by affecting the structure of the SC on the skin surface. Therefore, this study might provide an efficient way to improve the topical delivery of POD to the epidermis of the skin, thereby enhancing the therapeutic effect of genital warts.