Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, MP 470 003, India.
AAPS J. 2010 Jun;12(2):130-7. doi: 10.1208/s12248-009-9169-1. Epub 2010 Jan 15.
In this study, hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared and coated with chitosan and trimethyl chitosan (TMC) to evaluate the effect of coating material for nasal vaccine delivery. The developed formulations were characterized for size, zeta potential, entrapment efficiency, and mucin adsorption ability. Plain PLGA microparticles demonstrated negative zeta potential. However, coated microparticles showed higher positive zeta potential. Results indicated that TMC microparticles demonstrated substantially higher mucin adsorption when compared to chitosan-coated microparticles and plain PLGA microparticles. The coated and uncoated microparticles showed deposition in nasal-associated lymphoid tissue under fluorescence microscopy. The coated and uncoated microparticles were then administered intranasally to mice. Immune-adjuvant effect was determined on the basis of specific antibody titer observed in serum and secretions using enzyme-linked immunosorbent assay. It was observed that coated particles showed a markedly increased anti-HBsAg titer as compared to plain PLGA microparticles, but the results were more pronounced with the TMC-coated PLGA microparticles.
在这项研究中,制备了负载乙肝表面抗原(HBsAg)的聚乳酸-共-羟基乙酸(PLGA)微球,并将其用壳聚糖和三甲基壳聚糖(TMC)进行涂层,以评估涂层材料对鼻内疫苗传递的效果。所开发的制剂的特征在于粒径、zeta 电位、包封效率和粘蛋白吸附能力。普通的 PLGA 微球表现出负的 zeta 电位。然而,涂层微球显示出更高的正 zeta 电位。结果表明,与壳聚糖涂层微球和普通 PLGA 微球相比,TMC 微球表现出更高的粘蛋白吸附能力。在荧光显微镜下,涂层和未涂层的微球在鼻相关淋巴组织中显示出沉积。然后将涂层和未涂层的微球通过鼻腔给予小鼠。基于酶联免疫吸附试验在血清和分泌物中观察到的特异性抗体滴度来确定免疫佐剂效应。结果表明,与普通 PLGA 微球相比,涂层颗粒显示出明显增加的抗 HBsAg 滴度,但 TMC 涂层的 PLGA 微球的效果更为明显。