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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14144-14150
Number of pages7
JournalACS Omega
Volume3
Issue number10
DOIs
StatePublished - Oct 25 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 American Chemical Society.

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