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Updated: Jul 17, 2025

Assembly and Characterization of Polyelectrolyte Complex Micelles

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Published on: March 2, 2020

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized by Polycationic Complexation.

Preye Agbana¹, Ji Eun Park¹, Piotr Rychahou²

¹Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.

Journal of Pharmaceutical Sciences

|September 6, 2023

Summary

This summary is machine-generated.

Stabilized ternary polypeptide nanoparticles (tPNPs) enhance carfilzomib delivery for solid cancers. These pH-responsive nanoparticles improve drug release and efficacy against resistant cancer cells.

Keywords:

Drug delivery Inclusion complex Polyion complex Polypeptide nanoparticles Self-assemblies pH-responsive drug release

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Published on: January 7, 2019

Area of Science:

Biomedical Engineering
Nanotechnology
Cancer Therapeutics

Background:

Carfilzomib (CFZ) is effective for multiple myeloma but limited in solid cancers due to poor solubility and stability.
Previous ternary polypeptide nanoparticles (tPNPs) improved CFZ delivery but required enhanced particle stability for sustained release.
Initial burst release from tPNPs necessitates improved stability for prolonged proteasome inhibition in vivo.

Purpose of the Study:

To stabilize CFZ-loaded tPNPs using polycations with varying pKa values.
To investigate the pH-dependent drug release kinetics and particle stability of stabilized tPNPs.
To evaluate the enhanced efficacy of stabilized tPNPs against CFZ-resistant cancer cells.

Main Methods:

Formation of CFZ-loaded tPNPs stabilized by polycation complexation.
Characterization of particle size and stability before and after freeze-drying.
Assessment of pH-dependent in vitro drug release profiles.
In vitro cytotoxicity and proteasome activity assays against cancer cells.

Main Results:

Polycation complexation stabilized the core of CFZ-loaded tPNPs, maintaining uniform particle size.
CFZ/tPNPs exhibited pH-dependent release, accelerating as acidity increased (pH < 6) while remaining stable at pH 7.4.
Stabilized tPNPs demonstrated improved in vitro bioactivity against CFZ-resistant cancer cells.

Conclusions:

Polycation-stabilized tPNPs offer a promising strategy to overcome CFZ limitations in solid cancers.
The pH-dependent release mechanism is advantageous for targeting acidic tumor microenvironments.
These findings support the potential of CFZ-loaded tPNPs in combination therapies for drug-resistant solid tumors.