Miltenyi Biotec GmbH, Bergisch Gladbach 51429, Germany; Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 329, Heidelberg 69120, Germany.
Department of Mechanical Engineering and Materials Science, Yale University, New Haven, Connecticut 06520-8286.
J Pharm Sci. 2017 Nov;106(11):3316-3327. doi: 10.1016/j.xphs.2017.06.013. Epub 2017 Jun 23.
Polymer nanoparticles (NP) are of escalating interest for their application as immune stimulatory pharmaceutics. The production of nanosized carrier systems is currently being widely investigated, but commonly used techniques, such as the double emulsion technique, are limited by shortcomings of low encapsulation efficiency and poor control over size distribution. In this study, the electrospray technique was successfully implemented and optimized to produce monodisperse 200-nm poly(lactide-co-glycolide) (PLGA) NP. For cytomegalovirus (CMV) pp65 and IE-1 peptides, a consistent encapsulation efficiency of approximately 85% was achieved. In vitro stimulation of peripheral blood mononuclear cells (PBMCs) from CMV donors using electrosprayed pp65 peptide-loaded NP revealed a significantly increased proliferation rate and frequency of antigen-specific CD8 T cells as compared to the soluble peptide. The results of this study demonstrate the suitability of the electrospray technique for production of monodisperse PLGA NP with high drug encapsulation efficiency as promising peptide-based vaccine carriers.
聚合物纳米粒子 (NP) 因其作为免疫刺激性药剂的应用而受到越来越多的关注。目前正在广泛研究纳米载体系统的生产，但常用的技术，如双重乳液技术，存在包封效率低和难以控制粒径分布等缺点。在这项研究中，成功实施并优化了电喷雾技术，以生产单分散 200nm 的聚（乳酸-共-乙醇酸）（PLGA）NP。对于巨细胞病毒 (CMV) pp65 和 IE-1 肽，实现了约 85%的一致包封效率。与可溶性肽相比，使用电喷雾 pp65 肽负载 NP 对 CMV 供体的外周血单核细胞 (PBMC) 进行体外刺激，显示出增殖率和抗原特异性 CD8 T 细胞的频率显著增加。这项研究的结果表明，电喷雾技术适合生产具有高药物包封效率的单分散 PLGA NP，是有前途的基于肽的疫苗载体。
