Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination
Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination
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DOI：
10.1208/pt0804081
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Hickey, Anthony J.
中科院分区：
文献类型：
--
作者：
Garmise, Robert J.;Staats, Herman F.;Hickey, Anthony J.
这些研究的目的是增强粘膜和全身抗体的产生，以响应作为干粉鼻疫苗制剂施用的完整灭活流感病毒的局部停留时间的增加。对适合鼻腔给药的喷雾冷冻干燥 (SFD) 颗粒进行了物理化学性质和稳定性的表征。与已发表的体外数据相比，粘膜粘附化合物（MA）对疫苗粉末在大鼠鼻腔停留时间的影响进行了表征，并引发了免疫反应。 SFD颗粒(D-50=26.9μm)为球形，比表面积为1.25m(2)/g。热分析表明，SFD 粉末是无定形的，并且在各种储存条件下相对于液体制剂表现出更高的稳定性。体外物理化学研究和体内闪烁扫描成像实验表明，海藻酸钠（SA）和羧甲基纤维素高分子量（CMC-HMW）粉末制剂最显着地增加了挪威棕色大鼠的停留时间。初始给药后，在存在 CMC-HMW、SA 和羟丙基甲基纤维素 (HPMC-HMW) 的情况下，肌内递送提供了与不含 MA 的鼻内 (IN) 粉末相当的血清抗体滴度，以及在加强后除含有壳聚糖的 IN 粉末以外的所有制剂。在初次接种疫苗后，IN 液体提供了与所有 IN 粉末相当的血清抗体滴度，并且在加强免疫后，其血清抗体滴度明显高于含壳聚糖的 IN 粉末。停留时间研究和免疫反应之间的趋势是一致的；然而，粉末和液体制剂之间没有观察到统计学上的显着差异。结论是，干粉鼻疫苗，特别是在海藻酸钠存在下施用，可引起增强的血清和粘膜抗体反应。
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 mu m) 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.