LeClair Daniel A, Cranston Emily D, Lichty Brian D, Xing Zhou, Thompson Michael R
Department of Chemical Engineering, McMaster University, 1280 Main Street W., Hamilton, Ontario L8S 4L7, Canada.
McMaster Immunology Research Centre & Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street W., Hamilton, Ontario L8S 4L7, Canada.
ACS Biomater Sci Eng. 2018 May 14;4(5):1669-1678. doi: 10.1021/acsbiomaterials.8b00117. Epub 2018 Apr 10.
Current global vaccination programs are challenged by costs associated with vaccine cold chain storage and administration. A solid, thermally stable oral dosage form for vaccines would alleviate these costs but is difficult to produce due to general vaccine instability and the complication of bypassing the gastric barrier. We developed a novel consecutive spray drying method that is suitable for use with biologics and employs Eudragit L100 polymer as the enteric coating. More specifically, in step 1, recombinant replication deficient human type-5 adenovirus and vesicular stomatitis virus were encapsulated by spray drying with sugars from a water solution, and in step 2, the microparticles from step 1 were suspended in ethanol with Eudragit and spray dried again. Up to 25% of the starting material was fully encapsulated within the enteric coating, and encapsulation efficiency was largely dependent on spray gas flow rate and the solids concentration in the feed. After step 2, the coated vaccine-sugar particles maintained their thermostability and were slightly larger in size with a rugous surface morphology compared to the particles produced in step 1. The coated particles retained viral vector activity in vitro after 15 min incubation in 1 M HCl (simulating the stomach environment) and anhydrous ethanol (to dissolve the Eudragit outer shell). The production of dry, orally administered vaccine particles from consecutive spray drying offers the potential to remedy a number of vaccine storage, transportation, and administration limitations.
当前全球疫苗接种计划面临着与疫苗冷链储存和接种相关的成本挑战。一种固态、热稳定的口服疫苗剂型可以降低这些成本，但由于疫苗普遍不稳定以及绕过胃屏障的复杂性，这种剂型很难生产。我们开发了一种适用于生物制品的新型连续喷雾干燥方法，并采用聚丙烯酸树脂L100聚合物作为肠溶包衣。具体而言，在步骤1中，通过从水溶液中用糖类进行喷雾干燥来包封重组复制缺陷型人5型腺病毒和水疱性口炎病毒，在步骤2中，将步骤1中的微粒与聚丙烯酸树脂一起悬浮在乙醇中并再次进行喷雾干燥。高达25%的起始原料被完全包封在肠溶包衣内，包封效率在很大程度上取决于喷雾气体流速和进料中的固体浓度。步骤2之后，与步骤1中产生的颗粒相比，包衣的疫苗-糖颗粒保持了它们的热稳定性，并且尺寸略大，表面形态粗糙。在1 M盐酸（模拟胃环境）和无水乙醇（溶解聚丙烯酸树脂外壳）中孵育15分钟后，包衣颗粒在体外保留了病毒载体活性。通过连续喷雾干燥生产干燥的口服疫苗颗粒有可能弥补疫苗储存、运输和接种方面的一些限制。
