The encapsulation of biologics (peptides, proteins, nucleic acids) into nanocarriers to achieve novel therapeutic behavior has been envisioned for decades, but clinical translation has been hampered by complex production strategies. The methods that have been developed, such as liposomes or double emulsion techniques, are limited by low loading (the fraction of the total formulation mass composed of the biologic). To address this unmet need, we have developed a self-assembly process to form polymeric nanocarriers comprising a biologic in a hydrophilic core, encapsulated by a poly(lactic acid) shell, and stabilized by a poly(ethylene glycol) brush. Called “inverse Flash NanoPrecipitation”, the technique uses scalable processing steps to achieve biologic loadings that are 5-15x higher than values achieved for liposomes or the double emulsion process (9-27% versus &lt;2%).<br/><br/>While improved loading and scalable processing are both important metrics for formulations of biotherapeutics, it is also crucial that the biologic remains stable to processing and that suitable release profiles are achieved using the nanocarrier. We describe a detailed assessment of chemical and physical stability of several water-soluble compounds and model biologics in the process. We have characterized degradation and refolding behavior for therapeutics ranging from antibiotics to β-galactosidase using assorted techniques: HPLC, NMR, circular dichroism, SEC, and/or activity measurements. While robust proteins like lysozyme and horseradish peroxidase recovered full activity, β-galactosidase lost nearly all initial activity. We therefore detail an approach that seeks to stabilize sensitive proteins to the processing steps using depletion-driven attractions to reversibly cluster the biologic. In the second part of the talk, we highlight release profiles achieved as a function of nanocarrier composition. We describe the mechanism of release, the associated design principles, and discuss potential uses of the technology.

Nanocarrier design using inverse Flash NanoPrecipitation: Ensuring therapeutic stability and achieving controlled release of peptides and proteins

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.