Nanoscale carriers can be used to encapsulate peptides, proteins, and nucleotides, imparting beneficial therapeutic properties not exhibited by these biologics alone. For example, encapsulation can alter the biodistribution of the therapeutic or promote internalization by target cells. Lipid formulations and the double emulsion approach to form polymeric nanocarriers have been used for this purpose. However, their clinical use for administration of water-soluble therapeutics has been limited because high process losses pose an economic barrier, among other challenges. We have developed a process that addresses this limitation using sequential block copolymer assembly steps to encapsulate water-soluble therapeutics in a hydrophilic core, enclosed by a hydrophobic poly(lactic acid) shell. We ionically crosslink this core to stabilize it against osmotic forces and install a dense polymer brush, e.g. PEG, to impart desired surface properties. Called “inverse Flash NanoPrecipitation” (iFNP), the process achieves loadings that are 5-15x higher than liposomes or other polymeric nanocarriers. In the first part of this talk, we describe the processing steps and underlying mechanism of assembly. Use of these nanocarriers to achieve modified biodistribution or cell internalization demands an understanding of the nanocarrier stability in buffer and in the biological milieu. The properties of the crosslinked core and the hydrophobic shell will dictate the nature and extent of changes to the nanocarrier structure during incubation at physiological conditions. To guide iFNP nanocarrier design, we describe how the composition impacts the stability of size and surface charge on nanocarriers in buffer. Once stable nanocarriers have been produced, well-known surface modifications (charge, ligand conjugation, etc.) can be employed to modify distribution behavior in the desired manner. Finally, we detail the biodistribution of formulations with different surface charges in vivo using PET imaging in a mouse model.

Colloidal stability and biodistribution of polymeric nanocarriers encapsulating peptides and proteins produced by inverse Flash NanoPrecipitation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.