Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles
Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles
复制标题
DOI：
10.1016/j.jconrel.2012.12.002
复制
发表时间：
2013-03-10
影响因子：
10.8
通讯作者：
Prausnitz, Mark R.
中科院分区：
文献类型：
--
作者：
Choi, Hyo-Jick;Bondy, Brian J.;Prausnitz, Mark R.
使用涂有疫苗的微针贴片进行免疫接种提供了简化疫苗接种物流和增加疫苗免疫原性的前景。本研究考察了流感疫苗在微针包衣过程中的稳定性，重点考察了包衣制剂辅料的作用。使用含有粘度增强剂和表面活性剂的涂层制剂获得厚的、均匀的涂层，但这些制剂在涂层后保留很少的功能性疫苗血凝素（HA）活性。仅海藻糖制剂中的疫苗包衣保留了约40-50%的疫苗活性，这是一个显著的改进。假设在仅含海藻糖的制剂中观察到的部分病毒活性丧失来自渗透压诱导的疫苗不稳定。我们发现，包括粘度增强剂，羧甲基纤维素，克服了这种影响，并保留了完整的疫苗活性的清洗和等离子体清洁钛表面。向海藻糖制剂中添加聚合物表面活性剂Lutrol（R）micro 68产生了疫苗涂层的相变，例如结晶和相分离，这与额外的疫苗活性损失相关，特别是当在亲水性等离子体清洁的钛上涂覆时。同样，粘度增强剂的添加抑制了干燥过程中表面活性剂诱导的相变，这通过小鼠免疫后抗体应答和存活率的体内评估得到证实。我们得出结论，海藻糖和粘度增强剂是有益的包衣辅料，但包括表面活性剂是有害的疫苗稳定性。(C)2012爱思唯尔有限公司版权所有。
Immunization using a microneedle patch coated with vaccine offers the promise of simplified vaccination logistics and increased vaccine immunogenicity. This study examined the stability of influenza vaccine during the microneedle coating process, with a focus on the role of coating formulation excipients. Thick, uniform coatings were obtained using coating formulations containing a viscosity enhancer and surfactant, but these formulations retained little functional vaccine hemagglutinin ( HA) activity after coating. Vaccine coating in a trehalose-only formulation retained about 40-50% of vaccine activity, which is a significant improvement. The partial viral activity loss observed in the trehalose-only formulation was hypothesized to come from osmotic pressure-induced vaccine destabilization. We found that inclusion of a viscosity enhancer, carboxymethyl cellulose, overcame this effect and retained full vaccine activity on both washed and plasma-cleaned titanium surfaces. The addition of polymeric surfactant, Lutrol (R) micro 68, to the trehalose formulation generated phase transformations of the vaccine coating, such as crystallization and phase separation, which was correlated to additional vaccine activity loss, especially when coating on hydrophilic, plasma-cleaned titanium. Again, the addition of a viscosity enhancer suppressed the surfactant-induced phase transformations during drying, which was confirmed by in vivo assessment of antibody response and survival rate after immunization in mice. We conclude that trehalose and a viscosity enhancer are beneficial coating excipients, but the inclusion of surfactant is detrimental to vaccine stability. (C) 2012 Elsevier B.V. All rights reserved.