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
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.