LiCalsi C, Maniaci M J, Christensen T, Phillips E, Ward G H, Witham C
Dura Pharmaceuticals, San Diego, CA 92121, USA.
Vaccine. 2001 Mar 21;19(17-19):2629-36. doi: 10.1016/s0264-410x(00)00503-x.
Both the mortality rate for measles and the risks associated with injection continue to be high in the developing world. In response to the need for safe, cost-effective vaccine delivery technologies, a powder formulation of measles vaccine has been developed to test the feasibility of administering measles vaccine as an aerosol. The first challenge in aerosol formulation development is to produce fine particles without damaging the activity of the virus or inducing physical changes. In this study, live attenuated measles vaccine is micronized by jet milling to generate particle sizes appropriate for pulmonary delivery (1-5 microm). Milling does not induce detectable physical changes and significant viral potency is maintained. Potency retention of milled vaccine ranges from 31 to 89%, demonstrating that the standard dose of vaccine can easily be achieved. Following size reduction, particles are blended with an inert carrier to improve handling and aerosol dispersion. The measles vaccine formulation is dispersable, as shown by laser light particle size analysis of vaccine aerosols. Thus, evaluation of both the potency retention and the aerosol characteristics of the current formulation clearly demonstrates the feasibility of delivering measles vaccine as a powder aerosol for immunization.
在发展中世界，麻疹死亡率以及与注射相关的风险仍然很高。为满足对安全、具有成本效益的疫苗递送技术的需求，已开发出麻疹疫苗的粉末制剂，以测试将麻疹疫苗作为气雾剂给药的可行性。气雾剂制剂开发中的首要挑战是生产细颗粒，同时不损害病毒活性或引发物理变化。在本研究中，减毒活麻疹疫苗通过气流粉碎进行微粉化，以产生适合肺部给药的粒径（1-5微米）。粉碎不会引起可检测到的物理变化，并且能保持显著的病毒效力。研磨后疫苗的效力保留率在31%至89%之间，表明可以轻松达到标准疫苗剂量。粒径减小后，将颗粒与惰性载体混合，以改善处理和气雾剂分散性。如疫苗气雾剂的激光粒度分析所示，麻疹疫苗制剂是可分散的。因此，对当前制剂的效力保留率和气雾剂特性的评估清楚地证明了将麻疹疫苗作为粉末气雾剂进行免疫接种的可行性。
