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弹性脂质体介导的乙肝经皮免疫

Elastic liposomes mediated transcutaneous immunization against Hepatitis B.

作者信息

Mishra Dinesh, Dubey Vaibhav, Asthana Abhay, Saraf D K, Jain N K

机构信息

Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470003, India.

出版信息

Vaccine. 2006 May 29;24(22):4847-55. doi: 10.1016/j.vaccine.2006.03.011. Epub 2006 Mar 15.

Abstract

Transcutaneous immunization presents a major challenge due to poor permeability of antigens through the skin barrier. To overcome this limitation ultradeformable lipid vesicles, the elastic liposomes, could be a better module for transcutaneous delivery of these proteinaceous antigens. In the present investigation Hepatitis B surface antigen (HBsAg)-loaded elastic liposomes were utilized as a mode for enhanced immunity against the antigen. Elastic liposomes were prepared by conventional rotary evaporation method and characterized for various parameters such as vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, stability and in vitro release pattern. Ex vivo cellular uptake and fluorescence studies were also conducted. In vivo studies were performed by measuring the immune response elicited by topically applied HBsAg-loaded elastic liposomes and compared to the intramuscularly administered alum-adsorbed HBsAg solution, topically applied plain HBsAg solution and physical mixture of HBsAg and elastic liposomes. Results indicate that transcutaneous immunization via elastic liposomes induces robust systemic and mucosal antibody response against HBsAg as compared to other formulations. The fluorescence microscopy results suggest prominent skin permeation and biodistribution, demonstrating efficient delivery of antigens to the immunocompetent Langerhans cells (LC) and lymphatics. The elastic liposomal formulation provides higher entrapment efficiency, enhanced penetration and effective immunoadjuvant property justifying its potential for improved vaccine delivery.

摘要

由于抗原透过皮肤屏障的渗透性较差,经皮免疫面临重大挑战。为克服这一限制,超可变形脂质体,即弹性脂质体,可能是经皮递送这些蛋白质抗原的更好载体。在本研究中,负载乙型肝炎表面抗原(HBsAg)的弹性脂质体被用作增强针对该抗原免疫力的一种方式。弹性脂质体通过常规旋转蒸发法制备,并对其各种参数进行了表征,如囊泡形状和表面形态、大小和大小分布、包封率、弹性、浊度、稳定性和体外释放模式。还进行了体外细胞摄取和荧光研究。通过测量局部应用负载HBsAg的弹性脂质体引发的免疫反应进行体内研究,并与肌肉注射明矾吸附的HBsAg溶液、局部应用普通HBsAg溶液以及HBsAg与弹性脂质体的物理混合物进行比较。结果表明,与其他制剂相比,通过弹性脂质体进行经皮免疫可诱导针对HBsAg的强大全身和黏膜抗体反应。荧光显微镜结果表明有明显的皮肤渗透和生物分布,证明抗原能有效递送至具有免疫活性的朗格汉斯细胞(LC)和淋巴管。弹性脂质体制剂具有更高的包封率、增强的渗透性和有效的免疫佐剂特性,证明其在改善疫苗递送方面具有潜力。

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