Guo Fang, Wang Jinping, Ma Man, Tan Fengping, Li Nan
Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, People's Republic of China.
J Mater Sci Mater Med. 2015 Apr;26(4):175. doi: 10.1007/s10856-015-5487-2. Epub 2015 Apr 1.
Liposomal carriers for topical drug delivery have been studied since the 1980s and have evoked a considerable interest. However, the conventional liposomes do not deeply penetrate into the skin and remain confined to the outer layer of SC. In order to increase skin targeting of ketoconazole (KCZ), a hydrophobic broad-spectrum antifungal agent, this study describes novel lipid vesicles as nano-carriers for topical delivery. In this paper, lipid vesicular systems including conventional liposomes (CL), ethosomes, deformable liposomes (DL) and ethanol-containing deformable liposomes (DEL) were prepared as nano-carriers for KCZ, respectively. Sodium dodecyl sulfate [SDS, 0.08 % (W/V)] was used as edge activator for DL and DEL preparation. Characterization of the vesicles was based on particle size, zeta potential, entrapment efficiency and transmission electron microscopy (TEM). In addition, in vitro permeation profile was obtained using vertical diffusion Franz cells by porcine skin. The in vivo accumulation of KCZ was also evaluated in rat skin. Confocal microscopy was performed to visualize the penetration of fluorescently labeled vesicles into skin. All of the lipid vesicles showed almost spherical structures with low polydispersity index (PDI < 0.3) and nano-metric size (no more than 160 nm). The results demonstrated that DEL dramatically improved both in vitro and in vivo skin deposition compared to the CLs (P < 0.05), which was further confirmed by confocal laser scanning microscopy study. In vivo pharmacodynamic studies showed DEL improved antifungal activity against Candida albicans in shorter duration of time. Therefore, based on present study, the novel nano-carrier DEL capable of enhancing skin target effect and forming a micro drug-depot could serve as an effective skin targeting delivery for KCZ as an anti-fungal agent in local therapy.
自20世纪80年代以来，用于局部给药的脂质体载体就已被研究，并引起了广泛关注。然而，传统脂质体无法深入渗透到皮肤中，而是局限于角质层的外层。为了提高疏水性广谱抗真菌剂酮康唑（KCZ）的皮肤靶向性，本研究描述了新型脂质囊泡作为局部给药的纳米载体。本文分别制备了包括传统脂质体（CL）、醇质体、可变形脂质体（DL）和含乙醇可变形脂质体（DEL）在内的脂质囊泡系统作为KCZ的纳米载体。十二烷基硫酸钠[SDS，0.08%（W/V）]用作DL和DEL制备的边缘活化剂。基于粒径、zeta电位、包封率和透射电子显微镜（TEM）对囊泡进行表征。此外，使用垂直扩散Franz细胞通过猪皮肤获得体外渗透曲线。还在大鼠皮肤中评估了KCZ的体内蓄积情况。进行共聚焦显微镜检查以观察荧光标记囊泡在皮肤中的渗透情况。所有脂质囊泡均呈现几乎球形的结构，多分散指数较低（PDI<0.3）且尺寸为纳米级（不超过160nm）。结果表明，与CL相比，DEL显著改善了体外和体内皮肤沉积（P<0.05），共聚焦激光扫描显微镜研究进一步证实了这一点。体内药效学研究表明，DEL在较短时间内提高了对白色念珠菌的抗真菌活性。因此，基于本研究，新型纳米载体DEL能够增强皮肤靶向作用并形成微药物库，可作为KCZ作为抗真菌剂在局部治疗中的有效皮肤靶向递送载体。
