Wilson David R, Mosenia Arman, Suprenant Mark P, Upadhya Rahul, Routkevitch Denis, Meyer Randall A, Quinones-Hinojosa Alfredo, Green Jordan J
Biomedical Engineering, Johns Hopkins University, Baltimore, 21231.
Translational Tissue Engineering Center, Johns Hopkins of Medicine, Baltimore, 21231.
J Biomed Mater Res A. 2017 Jun;105(6):1813-1825. doi: 10.1002/jbm.a.36033. Epub 2017 Apr 12.
Translation of biomaterial-based nanoparticle formulations to the clinic faces significant challenges including efficacy, safety, consistency and scale-up of manufacturing, and stability during long-term storage. Continuous microfluidic fabrication of polymeric nanoparticles has the potential to alleviate the challenges associated with manufacture, while offering a scalable solution for clinical level production. Poly(beta-amino esters) (PBAE)s are a class of biodegradable cationic polymers that self-assemble with anionic plasmid DNA to form polyplex nanoparticles that have been shown to be effective for transfecting cancer cells specifically in vitro and in vivo. Here, we demonstrate the use of a microfluidic device for the continuous and scalable production of PBAE/DNA nanoparticles followed by lyophilization and long term storage that results in improved in vitro efficacy in multiple cancer cell lines compared to nanoparticles produced by bulk mixing as well as in comparison to widely used commercially available transfection reagents polyethylenimine and Lipofectamine® 2000. We further characterized the nanoparticles using nanoparticle tracking analysis (NTA) to show that microfluidic mixing resulted in fewer DNA-free polymeric nanoparticles compared to those produced by bulk mixing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1813-1825, 2017.
基于生物材料的纳米颗粒制剂向临床转化面临着重大挑战，包括疗效、安全性、一致性、扩大生产规模以及长期储存期间的稳定性。连续微流体制备聚合物纳米颗粒有潜力缓解与制造相关的挑战，同时为临床规模生产提供可扩展的解决方案。聚（β - 氨基酯）（PBAE）是一类可生物降解的阳离子聚合物，它与阴离子质粒DNA自组装形成多聚体纳米颗粒，已证明这些纳米颗粒在体外和体内对特异性转染癌细胞有效。在此，我们展示了使用微流控装置连续且可扩展地生产PBAE/DNA纳米颗粒，随后进行冻干和长期储存，与通过批量混合生产的纳米颗粒以及与广泛使用的市售转染试剂聚乙烯亚胺和Lipofectamine® 2000相比，这导致在多种癌细胞系中体外疗效得到改善。我们进一步使用纳米颗粒跟踪分析（NTA）对纳米颗粒进行表征，以表明与批量混合生产的纳米颗粒相比，微流控混合产生的无DNA聚合物纳米颗粒更少。© 2017威利期刊公司。《生物医学材料研究杂志》A部分：第105A卷：1813 - 1825页，2017年。
