van der Kooij Renée S, Steendam Rob, Zuidema Johan, Frijlink Henderik W, Hinrichs Wouter L J
Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
InnoCore Pharmaceuticals, L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands.
Pharmaceutics. 2021 Nov 3;13(11):1854. doi: 10.3390/pharmaceutics13111854.
For many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provides for both administrations could greatly improve the convenience and vaccinee's compliance. In this study, we developed parenterally injectable core-shell microspheres with a delayed pulsatile release profile that could serve as the booster in such a vaccine formulation. These microspheres contained bovine serum albumin (BSA) as the model antigen and poly(dl-lactide--glycolide) (PLGA) with various dl-lactide:glycolide monomer ratios as the shell material. Highly monodisperse particles with different particle characteristics were obtained using a microfluidic setup. All formulations exhibited a pulsatile in vitro release of BSA after an adjustable lag time. This lag time increased with the increasing lactide content of the polymer and ranged from 3 to 7 weeks. Shell thickness and bovine serum albumin loading had no effect on the release behavior, which could be ascribed to the degradation mechanism of the polymer, with bulk degradation being the main pathway. Co-injection of the core-shell microspheres together with a solution of the antigen that serves as the primer would allow for the desired biphasic release profile. Altogether, these findings show that injectable core-shell microspheres combined with a primer are a promising alternative for the current multiple-injection vaccines.
对于许多疫苗而言，需要多次注射才能赋予针对目标病原体的保护性免疫。这些注射通常包括初次接种，随后在几周或几个月后进行疫苗加强接种。一种能同时实现这两种接种的单剂量疫苗制剂可极大地提高便利性和接种者的依从性。在本研究中，我们开发了具有延迟脉冲释放特性的可注射的核壳微球，可作为此类疫苗制剂中的加强剂。这些微球含有牛血清白蛋白（BSA）作为模型抗原，并以不同丙交酯：乙交酯单体比例的聚（dl-丙交酯-乙交酯）（PLGA）作为壳材料。使用微流控装置获得了具有不同颗粒特性的高度单分散颗粒。所有制剂在可调节的滞后时间后均呈现出BSA的脉冲式体外释放。该滞后时间随聚合物丙交酯含量的增加而增加，范围为3至7周。壳厚度和牛血清白蛋白负载量对释放行为没有影响，这可归因于聚合物的降解机制，其中本体降解是主要途径。将核壳微球与用作初次接种的抗原溶液共同注射可实现所需的双相释放特性。总之，这些发现表明，可注射的核壳微球与初次接种剂相结合是当前多次注射疫苗的一种有前景的替代方案。
