Continuous microfluidic assembly of biodegradable poly(beta‐amino ester)/DNA nanoparticles for enhanced gene delivery

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 all...

Full description

Saved in:
Bibliographic Details
Published in:Journal of biomedical materials research. Part A 2017-06, Vol.105 (6), p.1813-1825
Main Authors: Wilson, David R., Mosenia, Arman, Suprenant, Mark P., Upadhya, Rahul, Routkevitch, Denis, Meyer, Randall A., Quinones‐Hinojosa, Alfredo, Green, Jordan J.
Format: Article
Language:English
Subjects:
Biodegradability
Cancer
Cell Line, Tumor
Deoxyribonucleic acid
DNA - administration & dosage
DNA - genetics
Effectiveness
Equipment Design
Esters
Freeze Drying
gene delivery
Gene Transfer Techniques
Humans
hydrodynamic focusing
In vitro testing
Lab-On-A-Chip Devices
microfluidic
Microfluidics
nanoparticle
nanoparticle tracking analysis
Nanoparticles
Nanoparticles - chemistry
Plasmids - administration & dosage
Plasmids - genetics
polymer
Polymers - chemistry
Transfection - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1549-3296
1552-4965
DOI:10.1002/jbm.a.36033