Garmise Robert J, Staats Herman F, Hickey Anthony J
School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7360 Kerr Hall Room 1310, Chapel Hill, NC 27599, USA.
AAPS PharmSciTech. 2007 Oct 12;8(4):E81. doi: 10.1208/pt0804081.
The purpose of these studies was to enhance mucosal and systemic antibody production in response to increased local residence time of a whole inactivated influenza virus administered as a dry powder nasal vaccine formulation. Spray-freeze-drying (SFD) particles suitable for nasal delivery were characterized for physico-chemical properties and stability. Mucoadhesive compounds (MA) were characterized for their effects on nasal residence time of vaccine powders in rats compared with published in vitro data and elicited immune responses. SFD particles (D(50) = 26.9 microm) were spherical with a specific surface area of 1.25 m(2)/g. Thermal analysis indicated SFD powders were amorphous and demonstrated improved stability with respect to liquid formulations under various storage conditions. In vitro physico-chemical studies and in vivo scintigraphic imaging experiments indicated sodium alginate (SA) and carboxymethylcellulose-high molecular weight (CMC-HMW) powder formulations most significantly increased residence time in Brown Norway rats. Intramuscular delivery provided equivalent serum antibody titers to intranasal (IN) powder without MA, in the presence of CMC-HMW, SA, and hydroxypropyl methylcellulose (HPMC-HMW) after initial dosing and all formulations except IN powder with chitosan after boosting. IN liquid provided equivalent serum antibody titers to all IN powders after the initial vaccination and significantly greater serum antibody titers than IN powder with chitosan after boosting. Trends were consistent between residence time studies and immune response; however, no statistically significant differences between powder and liquid formulations were observed. It was concluded that enhanced serum and mucosal antibody responses were elicited by a dry powder nasal vaccine, specifically, administered in the presence of sodium alginate.
这些研究的目的是，通过增加以干粉鼻用疫苗制剂形式给药的全灭活流感病毒在局部的停留时间，来提高黏膜和全身抗体的产生。对适用于鼻腔给药的喷雾冷冻干燥（SFD）颗粒的物理化学性质和稳定性进行了表征。与已发表的体外数据相比，对黏膜粘附化合物（MA）在大鼠体内对疫苗粉末鼻腔停留时间的影响及其引发的免疫反应进行了表征。SFD颗粒（D(50)=26.9微米）呈球形，比表面积为1.25平方米/克。热分析表明，SFD粉末为无定形，并且在各种储存条件下相对于液体制剂显示出更高的稳定性。体外物理化学研究和体内闪烁成像实验表明，海藻酸钠（SA）和羧甲基纤维素-高分子量（CMC-HMW）粉末制剂最显著地增加了在挪威棕色大鼠体内的停留时间。在初次给药后以及加强免疫后除含壳聚糖的鼻内（IN）粉末外的所有制剂中，肌肉注射产生的血清抗体滴度与不含MA的鼻内（IN）粉末相当。初次接种疫苗后，鼻内液体产生的血清抗体滴度与所有鼻内粉末相当，加强免疫后，其血清抗体滴度显著高于含壳聚糖的鼻内粉末。停留时间研究和免疫反应之间的趋势是一致的；然而，未观察到粉末制剂和液体制剂之间有统计学上的显著差异。得出的结论是，干粉鼻用疫苗，特别是在海藻酸钠存在的情况下给药，可引发增强的血清和黏膜抗体反应。
