Synthesis and Purification of Homogeneous Lipid-Based Peptide Nanocarriers by Overcoming Phospholipid Ester Hydrolysis

Schnorenberg, Mathew R.; Yoo, Sang Pil; Tirrell, Matthew V.; LaBelle, James L.

doi:10.1021/acsomega.8b01772

Synthesis and Purification of Homogeneous Lipid-Based Peptide Nanocarriers by Overcoming Phospholipid Ester Hydrolysis

Journal Article · Thu Oct 25 00:00:00 EDT 2018 · ACS Omega

DOI:https://doi.org/10.1021/acsomega.8b01772· OSTI ID:1735938

Schnorenberg, Mathew R. ^[1]; Yoo, Sang Pil ^[2]; Tirrell, Matthew V. ^[1]; ^[2]

Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
Univ. of Chicago, IL (United States)

Despite the therapeutic promise of phospholipid-based nanocarriers, a major obstacle to their widespread clinical translation is a susceptibility to fatty acid ester hydrolysis, leading to lack of quality control and inconsistencies in self-assembly formulations. Using electrospray ionization mass spectrometry fragmentation in combination with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we have demonstrated a method to detect hydrolysis of one or both of the fatty acid esters in a PEGylated phospholipid, DSPE-PEG, in conditions commonly applied during nanocarrier production. Because such carriers are increasingly being used to deliver peptide-based therapeutics, we further investigated the hydrolysis of phospholipid esters in conditions used for solid-phase peptide synthesis and high-performance liquid chromatography of peptides. We ultimately detail a synthetic strategy to reliably produce pure phospholipid–peptide bioconjugates (peptide amphiphiles), while avoiding unintended or unnoticed hydrolyzed byproducts that could lead to polymorphic nanotherapeutics with dampened therapeutic efficacy. We believe that such an approach could help standardize phospholipid–peptide-based therapeutic development, testing, and clinical translation.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH); National Science Foundation (NSF); USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1735938

Journal Information:: ACS Omega, Journal Name: ACS Omega Journal Issue: 10 Vol. 3; ISSN 2470-1343

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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