Recent Progress in Polyion Complex Nanoparticles with Enhanced Stability for Drug Delivery

Polyion complex (PIC) nanoparticles, including PIC micelles and PICsomes, are typically composed of poly(ethylene glycol) block copolymers coupled with oppositely charged polyelectrolytes or therapeutic agents via electrostatic interaction. Due to a simple and rapid preparation process with high drug-loading efficiency, PIC nanoparticles are beneficial to maintaining the chemical integrity and high biological activity of the loaded drugs. However, the stability of PIC nanoparticles can be disrupted in high-ionic-strength solutions because electrostatic interaction is the DRIVING force; these disruptions can thus impair drug delivery. Herein, we summarize the advances in the use of PIC nanoparticles for delivery of charged drugs, focusing on the different chemical and physical strategies employed to enhance their stability, including enhancing the charge density, crosslinking, increasing hydrophobic interactions, forming hydrogen bonds, and the development of PIC-based gels. In particular, we describe the use of PIC nanoparticles to load peptide antibiotics targeting antibiotic-resistant and biofilm-related diseases and the use of nanoparticles that load chemotherapeutics and gaseous donors for cancer treatment. Furthermore, the application of PIC nanoparticles as magnetic resonance imaging contrast agents is summarized for the first time. Therefore, this review is of great significance for advances in the use of polymeric nanoparticles for functional drug delivery.