Ternary Polypeptide Nanoparticles with Improved Encapsulation, Sustained Release, and Enhanced In Vitro Efficacy of Carfilzomib

Preye Agbana, Min Jae Lee, Piotr Rychahou, Kyung Bo Kim, Younsoo Bae

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Purpose: To develop a new nanoparticle formulation for a proteasome inhibitor Carfilzomib (CFZ) to improve its stability and efficacy for future in vivo applications. Methods: CFZ-loaded ternary polypeptide nanoparticles (CFZ/tPNPs) were prepared by using heptakis(6-amino-6-deoxy)-β-cyclodextrin(hepta-hydrochloride) (HaβCD) and azido-poly(ethylene glycol)-block-poly(L-glutamic acid sodium salt) (N3-PEG-PLE). The process involved ternary (hydrophobic/ionic/supramolecular) interactions in three steps: 1) CFZ was entrapped in the cavity of HaβCD by hydrophobic interaction, 2) the drug-cyclodextrin inclusion complexes were mixed with N3-PEG-PLE to form polyion complex nanoparticles, and 3) the nanoparticles were modified with fluorescent dyes (AFDye 647) for imaging and/or epithelial cell adhesion molecule (EpCAM) antibodies for cancer cell targeting. CFZ/tPNPs were characterized for particle size, surface charge, drug release, stability, intracellular uptake, proteasome inhibition, and in vitro cytotoxicity. Results: tPNPs maintained an average particle size of 50 nm after CFZ entrapment, EpCAM conjugation, and freeze drying. tPNPs achieved high aqueous solubility of CFZ (>1 mg/mL), sustained drug release (t1/2 = 6.46 h), and EpCAM-mediated cell targeting, which resulted in increased intracellular drug accumulation, prolonged proteasome inhibition, and enhanced cytotoxicity of CFZ in drug-resistant DLD-1 colorectal cancer cells. Conclusions: tPNPs improved stability and efficacy of CFZ in vitro, and these results potentiate effective cancer treatment using CFZ/tPNPs in future vivo studies.

Original languageEnglish
Article number213
JournalPharmaceutical Research
Issue number11
StatePublished - Nov 1 2020

Bibliographical note

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.


  • cell targeting
  • colorectal cancer
  • drug delivery
  • drug resistance
  • polypeptide nanoparticles
  • proteasome inhibitors

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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