Mechanism of bacitracin permeation enhancement through the skin and cellular membranes from an ethosomal carrier
Mechanism of bacitracin permeation enhancement through the skin and cellular membranes from an ethosomal carrier
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DOI：
10.1016/j.jconrel.2003.10.014
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发表时间：
2004-02-10
影响因子：
10.8
通讯作者：
Touitou, E
中科院分区：
文献类型：
--
作者：
Godin, B;Touitou, E
本工作的主要目的是研究杆菌肽--一种模型多肽抗生素--从乙醇小体的真皮和细胞内给药。用扫描电子显微镜、透射电子显微镜、差示扫描量热法、动态光散射法和超速离心法分别对杆菌肽和荧光标记杆菌肽(FITC-Bac)乙醇微球的形态、片层性质、流动性、粒径分布和包封率进行了表征。激光共聚焦扫描显微镜(CLSM)实验表明，乙醇小体促进了抗生素和磷脂在培养的3T3瑞士白化小鼠成纤维细胞中的共渗透。这些结果得到了荧光激活细胞分选(FACS)实验数据的证实，表明乙醇小体穿透细胞膜，释放细胞内被包裹的分子。此外，还重点研究了FITC-Bac在体外和体内通过人身体和大鼠皮肤的渗透行为。这些研究表明，抗菌肽通过角质层(SC)的角质间脂域进入皮肤深层。在体外实验中，封闭对药物从乙醇体透皮的情况没有影响。有效地将抗生素从乙醇体用药输送到皮肤深层可能是非常有益的，减少了可能的副作用和与全身治疗相关的其他缺点。此外，可以考虑使用乙醇给药系统来治疗一些皮肤感染，这需要在细胞内给药，药物必须绕过两个屏障：SC和细胞膜。(C)2003爱思唯尔B.V.保留所有权利。
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. (C) 2003 Elsevier B.V. All rights reserved.