The development of stable influenza vaccine powder formulations for new needle-free dosage forms
The development of stable influenza vaccine powder formulations for new needle-free dosage forms
复制标题
新型无针剂型的稳定流感疫苗粉末制剂的开发
DOI：
--
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
H. Frijlink
中科院分区：
文献类型：
--
作者：
J. D. Jonge;Jean‐Pierre Amorij;W. Hinrichs;J. Wilschut;A. Huckriede;H. Frijlink
流感病毒小体是重组的流感病毒包膜，可用作疫苗或作为治疗分子的细胞递送载体系统。在这里，我们提出了一种使用无定形菊糖基质作为稳定剂，通过冷冻干燥(冻干)来产生稳定的干粉制剂的流感病毒小体的方法。在菊粉存在下，病毒小体的结构完整性和融合活性在冷冻干燥过程中得到完全保存。例如，在菊粉存在下的冻干过程中，保持了病毒小体的免疫学性质，即体外HA效力和体内免疫原性。此外，与分散在缓冲液中的病毒体相比，菊粉配制的病毒体在储存时显示出显著延长了HA效力的保存时间。此外，在菊粉存在下的冻干过程中和随后的储存过程中，病毒小体调节细胞大分子输送的能力保持不变。具体地说，当分散在缓冲液中时，包裹有质粒DNA的病毒体在6周内完全失去了转染性，而它们的转染性在掺入菊粉基质后至少保持了12周。因此，在菊粉作为稳定剂的存在下，含有和没有包裹大分子的流感病毒小体的货架期都大大延长。将流感病毒小体制成干粉有利于储存和运输，并提供了开发无针剂型的可能性，例如用于口服、鼻腔、肺部或经皮给药。
Influenza virosomes are reconstituted influenza virus envelopes that may be used as vaccines or as carrier systems for cellular delivery of therapeutic molecules. Here we present a procedure to generate influenza virosomes as a stable dry-powder formulation by freeze-drying (lyophilization) using an amorphous inulin matrix as a stabilizer. In the presence of inulin the structural integrity and fusogenic activity of virosomes were fully preserved during freeze-drying. For example, the immunological properties of the virosomes, i.e. the HA potency in vitro and the immunogenic potential in vivo, were maintained during lyophilization in the presence of inulin. In addition, compared to virosomes dispersed in buffer, inulin-formulated virosomes showed substantially prolonged preservation of the HA potency upon storage. Also the capacity of virosomes to mediate cellular delivery of macromolecules was maintained during lyophilization in the presence of inulin and upon subsequent storage. Specifically, when dispersed in buffer, virosomes with encapsulated plasmid DNA lost their transfection activity completely within 6 weeks, whereas their transfection activity was fully preserved for at least 12 weeks after incorporation in an inulin matrix. Thus, in the presence of inulin as a stabilizing agent, the shelf-life of influenza virosomes with and without encapsulated macromolecules was considerably prolonged. Formulation of influenza virosomes as a dry-powder is advantageous for storage and transport and offers the possibility to develop needle-free dosage forms e.g. for oral, nasal, pulmonal, or dermal delivery.
登录
查看更多内容
影响因子：
56.9
作者：
Edwards, DA;Hanes, J;Langer, R
通讯作者：
Langer, R
影响因子：
4.4
作者：
I. Mbawuike;S. Pacheco;C. Acuna;Kirsten Switzer;Yongxin Zhang;G. Harriman
通讯作者：
I. Mbawuike;S. Pacheco;C. Acuna;Kirsten Switzer;Yongxin Zhang;G. Harriman
影响因子：
4.4
作者：
K. B. Renegar;P. Small
通讯作者：
K. B. Renegar;P. Small
肺泡巨噬细胞、血单核细胞和密度分级的肺泡巨噬细胞促进淋巴细胞增殖至丝裂原和抗原的能力不同。
DOI：
10.1164/arrd.1987.135.3.682
发表时间：
1987
期刊：
The American review of respiratory disease
影响因子：
--
作者：
Ferro,TJ;Kern,JA;Elias,JA;Kamoun,M;Daniele,RP;Rossman,MD
通讯作者：
Rossman,MD
影响因子：
3.9
作者：
Aksan, A;Toner, M
通讯作者：
Toner, M