Flash nanoprecipitation permits versatile assembly and loading of polymeric bicontinuous cubic nanospheres

Sharan Bobbala, Sean David Allen, Evan Alexander Scott*

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Polymeric bicontinuous nanospheres (BCNs) that are analogous to lipid cubosomes possess high internal surface area and porosity that can accommodate the loading of a wide range of hydrophobic and hydrophilic molecules for diverse applications. Self-assembly of BCNs has been reported using complex amphiphilic polymeric structures, with co-solvent dispersion being the only documented method of formation. Here, we report a simple amphiphilic diblock copolymer, poly(ethylene glycol)17-block-poly(propylene sulfide)75 (PEG17-bl-PPS75), to form BCNs using the rapid and scalable technique of flash nanoprecipitation (FNP). Dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryoTEM) verified low polydispersity and the formation of bicontinuous structures with internal aqueous channels, respectively. Small-angle X-ray scattering (SAXS) confirmed a primitive cubic (Im3m) internal organization for BCNs assembled by FNP. Both hydrophobic and hydrophilic molecules were effectively loaded into BCNs via FNP, and encapsulated payloads were found to release in controlled manner in aqueous solutions. Due to the oxidation-sensitivity of PPS, biologically relevant concentrations of reactive oxygen species could trigger payload release on demand. BCNs were found to be non-toxic and endocytosed by phagocytic cells. Furthermore, an in vitro functional assay showed BCNs co-loaded with antigen ovalbumin and adjuvant monophosphoryl lipid A (MPL) to promote peptide/MHCI surface presentation by dendritic cells, a critical step for vaccine formulations during immunization. In conclusion, FNP supports the facile and scalable assembly and loading of PEG-bl-PPS BCNs, making them an attractive nanoscale delivery vehicle for both hydrophilic and hydrophobic molecules.

Original languageEnglish (US)
Pages (from-to)5078-5088
Number of pages11
JournalNanoscale
Volume10
Issue number11
DOIs
StatePublished - Mar 21 2018

ASJC Scopus subject areas

  • Materials Science(all)

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