Shah Ruchi R, Dodd Stephanie, Schaefer Mary, Ugozzoli Mildred, Singh Manmohan, Otten Gillis R, Amiji Mansoor M, O'Hagan Derek T, Brito Luis A
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, 02115.
J Pharm Sci. 2015 Apr;104(4):1352-61. doi: 10.1002/jps.24337. Epub 2015 Jan 19.
Microfluidization is an established technique for preparing emulsion adjuvant formulations for use in vaccines. Although this technique reproducibly yields high-quality stable emulsions, it is complex, expensive, and requires proprietary equipment. For this study, we developed a novel and simple low shear process to prepare stable reproducible emulsions without the use of any proprietary equipment. We found this process can produce a wide range of differently sized emulsions based on the modification of ratios of oil and surfactants. Using this process, we prepared a novel 20-nm-sized emulsion that was stable, reproducible, and showed adjuvant effects. During evaluation of this emulsion, we studied a range of emulsions with the same composition all sized below 200; 20, 90, and 160 nm in vivo and established a correlation between adjuvant size and immune responses. Our studies indicate that 160-nm-sized emulsions generate the strongest immune responses.
微流化是一种用于制备疫苗中使用的乳液佐剂制剂的成熟技术。尽管该技术可重复性地产生高质量的稳定乳液，但它复杂、昂贵且需要专用设备。在本研究中，我们开发了一种新颖且简单的低剪切工艺，无需使用任何专用设备即可制备稳定的可重复乳液。我们发现，基于油和表面活性剂比例的调整，该工艺可以生产出各种不同尺寸的乳液。利用此工艺，我们制备了一种新型的20纳米大小的乳液，该乳液稳定、可重复且具有佐剂效应。在对该乳液进行评估期间，我们研究了一系列组成相同、尺寸均小于200纳米（体内为20、90和160纳米）的乳液，并建立了佐剂尺寸与免疫反应之间的相关性。我们的研究表明，160纳米大小的乳液能产生最强的免疫反应。
