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

Abstract:

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.

journal_name

Curr Drug Deliv

journal_title

Current drug delivery

authors

Salmanpour M,Saeed-Vaghefi M,Abolmaali SS,Tamaddon A

doi

10.2174/1567201817999201103195846

subject

Has Abstract

pub_date

2020-11-03 00:00:00

eissn

1567-2018

issn

1875-5704

pii

CDD-EPUB-111164

pub_type

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