Niu Jiangxiu, Yuan Ming, Wang Liye, Zhang Pei, Cui Xingang, Fan Yanli, Liu Xianghui, Wang Jucai
College of Food and Drug, Luoyang Normal University, Luoyang, Henan 471934, PR China.
College of Life Science, Luoyang Normal University, Luoyang, Henan 471934, PR China.
ACS Omega. 2025 Aug 26;10(35):40422-40434. doi: 10.1021/acsomega.5c05798. eCollection 2025 Sep 9.
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 ( < 0.001) and POD-TFs ( < 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.
鬼臼毒素（POD）是用于生殖器疣外部治疗的主要药物。然而，传统的POD酊剂常引起严重的全身不良反应，因为药物可通过皮肤吸收进入血液循环。因此，开发新的POD局部制剂以增强局部给药并减少全身吸收尤为重要。在此，制备并表征了负载POD的角蛋白功能化传递体（POD-KTFs），并评估了其皮肤渗透与沉积、皮内荧光分布以及对皮肤结构的影响。POD-KTFs的流体动力学直径和表面电位分别为183.1 nm和 -33.9 mV。扫描电子显微镜（SEM）图像表明POD-KTFs呈球形外观。X射线衍射（XRD）图谱证实POD在POD-KTFs中主要以无定形形式存在。有意义的是，与POD酊剂和负载POD的传递体（POD-TFs）相比，POD-KTFs使POD在猪耳皮肤中的沉积分别增加了2.14倍和l.80倍，而POD在POD-KTFs中的透皮渗透率明显低于POD酊剂（<0.001）和POD-TFs（<0.01）。以香豆素-6作为荧光探针，皮肤切片的荧光成像显示POD-KTFs主要分布在表皮中。此外，POD-TFs可通过影响皮肤表面角质层（SC）的结构促进药物穿过SC。因此，本研究可能为改善POD向皮肤表皮的局部递送提供一种有效方法，从而提高生殖器疣的治疗效果。
