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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Sterically Stabilized Polyionic Complex Nanogels of Chitosan Lysate and PEG-b-Polyglutamic Acid Copolymer for the Delivery of Irinotecan Active Metabolite (SN-38)

Author(s): Mohsen Salmanpour, Mahvand Saeed-Vaghefi, Samira Sadat Abolmaali and Ali Mohamad Tamaddon*

Volume 18, Issue 6, 2021

Published on: 03 November, 2020

Page: [741 - 752] Pages: 12

DOI: 10.2174/1567201817999201103195846

Price: $65

Abstract

Background: Poly Ionic 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.

Objective: 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-carboxy anhydride polymerization of γ -benzyl L-glutamic acid, which is initiated by methoxy PEG-NH2 and successive debenzylation reaction.

Results: 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 the formation of homogeneous spherical particles with a mean size of 28 nm at the PEGb- 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 conditions. Conclusively, the well-tuned PIC nanogels are suggested as a potentially biocompatible nanocarrier for SN38 delivery.

Keywords: SN38, polyionic complex, nanogel, poly (L-amino acid), chitosan lysate, LMWC.

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