Godin B, Touitou E
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel.
J Control Release. 2004 Feb 10;94(2-3):365-79. doi: 10.1016/j.jconrel.2003.10.014.
The main objective of the present work was to investigate the dermal and intracellular delivery of bacitracin, a model polypeptide antibiotic, from ethosomes. Bacitracin and fluorescently labeled bacitracin (FITC-Bac) ethosomes were characterized for shape, lamellarity, fluidity, size distribution and entrapment capacity by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and ultracentrifugation, respectively. Confocal laser scanning microscopy (CLSM) experiments revealed that ethosomes facilitated the copenetration of antibiotic and phospholipid into cultured 3T3 Swiss albino mice fibroblasts. These results, confirmed by data obtained in fluorescent-activated cell sorting (FACS) experiments, suggest that ethosomes penetrate cellular membrane releasing the entrapped molecule within cells. Additional work was focused on skin permeation behavior of FITC-Bac from ethosomal systems in in vitro and in vivo experiments through human cadaver and rat skin, respectively. These studies demonstrated that the antibiotic peptide was delivered into deep skin layers through intercorneocyte lipid domain of stratum corneum (SC). Occlusion had no effect on the permeation profile of the drug from ethosomes in in vitro experiments. Efficient delivery of antibiotics to deep skin strata from ethosomal applications could be highly beneficial, reducing possible side effects and other drawbacks associated with systemic treatment. Furthermore, ethosomal delivery systems could be considered for the treatment of a number of dermal infections, requiring intracellular delivery of antibiotics, whereby the drug must bypass two barriers: the SC and the cell membrane.
本研究的主要目的是研究杆菌肽（一种典型的多肽抗生素）从醇质体中的皮肤递送和细胞内递送情况。分别通过扫描电子显微镜（SEM）、透射电子显微镜（TEM）、差示扫描量热法（DSC）、动态光散射（DLS）和超速离心法对杆菌肽和荧光标记的杆菌肽（FITC-Bac）醇质体的形状、片层结构、流动性、大小分布和包封能力进行了表征。共聚焦激光扫描显微镜（CLSM）实验表明，醇质体促进了抗生素和磷脂共同渗透到培养的3T3瑞士白化小鼠成纤维细胞中。荧光激活细胞分选（FACS）实验获得的数据证实了这些结果，表明醇质体穿透细胞膜并在细胞内释放包封的分子。额外的工作分别聚焦于通过人尸体皮肤和大鼠皮肤进行的体外和体内实验中，FITC-Bac从醇质体系统的皮肤渗透行为。这些研究表明，抗生素肽通过角质层（SC）的细胞间脂质区域递送至皮肤深层。在体外实验中，封闭对醇质体中药物渗透曲线没有影响。从醇质体应用中将抗生素有效递送至皮肤深层可能非常有益，可减少与全身治疗相关的可能副作用和其他缺点。此外，醇质体递送系统可考虑用于治疗多种需要抗生素细胞内递送的皮肤感染，其中药物必须绕过两个屏障：SC和细胞膜。
