Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

Abstract

Flash nanoprecipitation (FNP) has proven to be a powerful tool for the rapid and scalable assembly of solid-core nanoparticles from block copolymers. The process can be performed using a simple confined impingement jets mixer and provides an efficient and reproducible method of loading micelles with hydrophobic drugs. To date, FNP has not been applied for the fabrication of complex or vesicular nanoarchitectures capable of encapsulating hydrophilic molecules or bioactive protein therapeutics. Here, we present FNP as a single customizable method for the assembly of bicontinuous nanospheres, filomicelles and vesicular, multilamellar and tubular polymersomes from poly(ethylene glycol)-bl-poly(propylene sulfide) block copolymers. Multiple impingements of polymersomes assembled via FNP were shown to decrease vesicle diameter and polydispersity, allowing gram-scale fabrication of monodisperse polymersomes within minutes. Furthermore, we demonstrate that FNP supports the simultaneous loading of both hydrophobic and hydrophilic molecules respectively into the polymersome membrane and aqueous lumen, and encapsulated enzymes were found to be released and remain active following vesicle lysis. As an example application, theranostic polymersomes were generated via FNP that were dual loaded with the immunosuppressant rapamycin and a fluorescent dye to link targeted immune cells with the elicited immunomodulation of T cells. By expanding the capabilities of FNP, we present a rapid, scalable and reproducible method of nanofabrication for a wide range of nanoarchitectures that are typically challenging to assemble and load with therapeutics for controlled delivery and theranostic strategies.

Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded block copolymer micelles

“…As such, we would expect these micelles to have biodistributions similar to our previously reported data on intravenous injections of PEG‐ bl ‐PPS micelles . These data also support our previous findings that hydrophobic drugs can be loaded into PEG‐ bl ‐PPS micelles at therapeutically relevant concentrations without negatively impacting the assembled nanocarrier stability and morphology …”

Immunotheranostic Polymersomes Modularly Assembled from Tetrablock and Diblock Copolymers with Oxidation-Responsive Fluorescence

“…Several different methods are available for controlled assembly of PEG- bl -PPS, including solvent extraction, thin film hydration, and flash nanoprecipitation. 19, 23, 29 PEG- bl -PPS is non-immunogenic, allowing our nanocarriers to function as “blank slates” with an immunostimulatory potential based solely upon the selected molecules loaded inside. 19 PEG- bl -PPS block copolymers are therefore a unique tool for designing and engineering immunotheranostic delivery systems and incorporation of an innate sensor of disassembly into the copolymer chemistry could further enhance these capabilities.…”

Surface chemistry-mediated modulation of adsorbed albumin folding state specifies nanocarrier clearance by distinct macrophage subsets

“…1a; Supplementary Table 1; Supplementary Figure 1, 2). PS nanocarriers 17,18,20,21 were self-assembled from PEG-b-PPS diblock copolymers using flash nanoprecipitation [22][23][24][25] ( Supplementary Fig. 1-3).…”

“…2a-c. Nanostructure Preparation and Purification. PS nanocarriers were self-assembled from PEG-b-PPS BCPs ( Supplementary Table 1) using Flash Nanoprecipitation (FNP) as described previously 20,21 . Briefly, 20 mg of polymer was dissolved in 500 l of tetrahydrofuran (THF) (4.0% w/v), loaded into a 1 mL plastic disposable syringe, and was impinged against 500 l of sterile 1x PBS.…”