Effects of Organic Acids on Drug Release From Ternary Polypeptide Nanoparticles Entrapping Carfilzomib

Sharonda Jackson, Preye Agbana, Kyung Bo Kim, Younsoo Bae

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Carfilzomib (CFZ) is an FDA-approved proteasome inhibitor with antineoplastic properties against various cancers, yet its short blood retention time after intravenous injection (< 30 min) makes clinical applications limited to multiple myeloma. We previously developed ternary polypeptide nanoparticles (tPNPs) as a new nanoparticle formulation of CFZ to overcome these limitations. The formulation was prepared by polyion complexation between poly(ethylene glycol)-poly(L-glutamate) block copolymers (PEG-PLE) and CFZ-cyclodextrin (CD) inclusion complexes, where CDs were positively charged with 7 primary amines attached while PEG-PLE carried 100 carboxyl groups per polymer chain. Although tPNPs greatly improved biostability of CFZ, CFZ-loaded tPNPs (CFZ-tPNPs) still showed burst drug release and mediocre drug retention under physiological conditions. To address these issues, organic acids are tested as stabilizers in this study to improve particle stability and drug retention for tPNPs. Charge densities in the core of CFZ-tPNPs were optimized with selected organic acids such as citric acid (CA) and lactic acid (LA) at varying mixing ratios. Organic acids successfully maintained small particle size suitable for intravenous injection and drug delivery (diameters < 60 nm), improved CFZ solubility (> 1 mg/mL), allowed for lyophilization and easy reconstitution in various buffers, enhanced drug retention (> 60% post 24 h incubation), and suppressed burst drug release in the first 6 h following solubilization. These results demonstrate that organic acid stabilized tPNPs are useful as an injection formulation of CFZ, which may expand the utility of the proteasome inhibitor.

Original languageEnglish
Pages (from-to)1172-1177
Number of pages6
JournalJournal of Pharmaceutical Sciences
Issue number4
StatePublished - Apr 2022

Bibliographical note

Publisher Copyright:
© 2021 American Pharmacists Association


  • Carfilzomib
  • Complexation
  • Cyclodextrin
  • Drug delivery
  • Formulations
  • Polypeptide

ASJC Scopus subject areas

  • Pharmaceutical Science


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