title: Highly scalable, closed-loop synthesis of drug-loaded, layer-by-layer nanoparticles.
abstract: Layer-by-layer (LbL) self-assembly is a versatile technique from which multicomponent and stimuli-responsive nanoscale drug carriers can be constructed. Despite the benefits of LbL assembly, the conventional synthetic approach for fabricating LbL nanoparticles requires numerous purification steps that limit scale, yield, efficiency, and potential for clinical translation. In this report, we describe a generalizable method for increasing throughput with LbL assembly by using highly scalable, closed-loop diafiltration to manage intermediate purification steps. This method facilitates highly controlled fabrication of diverse nanoscale LbL formulations smaller than 150 nm composed from solid-polymer, mesoporous silica, and liposomal vesicles. The technique allows for the deposition of a broad range of polyelectrolytes that included native polysaccharides, linear polypeptides, and synthetic polymers. We also explore the cytotoxicity, shelf life and long-term storage of LbL nanoparticles produced using this approach. We find that LbL coated systems can be reliably and rapidly produced: specifically, LbL-modified liposomes could be lyophilized, stored at room temperature, and reconstituted without compromising drug encapsulation or particle stability, thereby facilitating large scale applications. Overall, this report describes an accessible approach that significantly improves the throughput of nanoscale LbL drug-carriers that show low toxicity and are amenable to clinically relevant storage conditions.
authors.affiliation: Institute for Integrative Cancer Research Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Santiago
authors.initials: S
authors.lastname: Correa
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Chemical Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Chemical Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Dreaden
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Kasper
authors.initials: K
authors.lastname: Renggli
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Aria
authors.initials: A
authors.lastname: Shi
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Chemical Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Gu
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Chemical Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Shopsowitz
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Chemical Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Mohiuddin A
authors.initials: MA
authors.lastname: Quadir
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Elana
authors.initials: E
authors.lastname: Ben-Akiva
authors.affiliation: Koch Institute for Integrative Cancer Research Department of Chemical Engineering Massachusetts Institute of Technology Cambridge, MA, 02139, USA.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
keywords: biomaterials; colloid chemistry; layer-by-layer nanoparticles; polymer engineering; scalable synthesis