Development of a thermostable microneedle patch for influenza vaccination.

Development of a thermostable microneedle patch for influenza vaccination.
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DOI:
10.1002/jps.24283
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发表时间:
2015-03
影响因子:
3.8
通讯作者:
Prausnitz MR
Prausnitz MR
中科院分区:
医学3区
文献类型:
--
作者:
Mistilis MJ;Bommarius AS;Prausnitz MR

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本研究的目的是开发用于流感疫苗的热稳定微针贴片制剂,其可以部分或完全从冷链中去除。在与微针贴片生产相关的疫苗干燥过程中,醋酸铵和HEPES缓冲盐稳定了流感疫苗,表面活性剂在干燥过程中几乎没有影响,干燥温度对疫苗稳定性的影响很小,与在不锈钢上干燥相比,在聚二甲基硅氧烷上干燥导致稳定性增加。许多赋形剂,主要是多糖和一些氨基酸,在干燥期间进一步稳定流感疫苗。在较长的储存时间范围内,稳定剂的组合保留了最多的疫苗活性。最后,在室温下储存6个月期间,用精氨酸和七葡萄糖酸钙配制的溶解性微针贴剂对所有三种季节性流感疫苗株没有显著的活性损失。我们的结论是,适当配制的微针贴片可以表现出显着的热稳定性,可以使流感疫苗的储存和分配冷链外。
The goal of this study is to develop thermostable microneedle patch formulations for influenza vaccine that can be partially or completely removed from the cold chain. During vaccine drying associated with microneedle patch manufacturing, ammonium acetate and HEPES buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane led to increased stability compared to drying on stainless steel. A number of excipients, mostly polysaccharides and some amino acids, further stabilized the influenza vaccine during drying. Over longer time scales of storage, combinations of stabilizers preserved the most vaccine activity. Finally, dissolving microneedle patches formulated with arginine and calcium heptagluconate had no significant activity loss for all three strains of seasonal influenza vaccine during storage at room temperature for six months. We conclude that appropriately formulated microneedle patches can exhibit remarkable thermostability that could enable storage and distribution of influenza vaccine outside the cold chain.
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