Sterically stabilized polyionic complex nanogels of chitosan lysate and PEG-b-polyglutamic acid copolymer for delivery of irinotecan active metabolite (SN-38)

Background:: Polyionic Complex (PIC) nanogels are promising delivery systems with numerous attractions such as simple, fast, and organic solvent-free particle formation and mild drug loading conditions. Among polyelectrolytes, poly (L-amino acid) copolymers such as poly (ethylene glycol)-block-poly (L-glutamic acid) copolymers (PEG-b-PGlu) are interesting biocompatible and biodegradable candidates bearing carboxylic acid functional groups. Objectives:: Aiming to solubilize and to preserve short-acting irinotecan active metabolite (SN38), sterically stabilized PIC nanogels were prepared through electrostatic charge neutralization between PEG-b-PGlu and chitosan lysate, a polycationic natural polymer obtained through digestion of chitosan by hydrogen peroxide oxidation and is soluble in a wide range of pH. Methods:: Synthesis of PEG-b-PGlu was accomplished by N-carboxyanhydride polymerization of γ -benzyl L-glutamic acid, which is initiated by methoxy PEG-NH2 and successive debenzylation reaction. Result:: The resulting block copolymer was characterized by FTIR, 1H-NMR, and Size Exclusion Chromatography (SEC). Self-assembling properties of the PIC nanogels were investigated by pyrene assay, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM), indicating formation of homogeneous spherical particles with a mean size of 28 nm at the PEG-b-PGlu concentrations/LMWC weight ratio of 5:1. Upon direct loading of SN38, the drug solubility enhanced more than 4×103 folds with a mean loading efficiency of 89% and the drug loading of 30%. PIC nanogels exhibited zeta potential of +1 mV, acceptable biocompatibility, and superior cytotoxicity in murine colorectal carcinoma (CT26 cell line) compared to free drug. Conclusion:: In addition, the PIC nanogels provided SN38 protection against hydrolytic degradation in physiologic condition. Conclusively, the well-tuned PIC nanogels are suggested as a potential biocompatible nanocarrier for SN38 delivery.

Tripartite polyionic complex (PIC) micelles as non-viral vectors for mesenchymal stem cell siRNA transfection

In this study, we demonstrate that PIC micelles readily form at physiological pH in the presence of siRNA and disassemble at a pH close to that of endosomes. Internalization of the micelles in primary MSC results in the down-regulation of Runx2.

Fabrication of Cell Outer Membrane Mimetic Surfaces on Chitosan Nanoparticles by Polyionic Complex and Template Polymerization

The polyanion of copolymer poly (2-methacryloyloxyethyl phosphorylcholine-co-methacrylic acid) (PMA30) was synthesized by free radical polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylic acid (MA). The synthesized PMA30 was assembled on chitosan (CS) surfaces formation of chitosan nanoparticles by polyionic complex. The chitosan nanoparticle was prepared using methacrylic acid (MA), 2-methacryloyloxyethyl phosphorylcholine (MPC) by template polymerization. The size distribution and structure properties of chitosan nanoparticles were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta potential. These results show that a cell outer membrane mimetic surface was formed on the chitosan nanoparticles, which provides an effective way to improve the biocompatibility of chitosan nanoparticles.