CYSTEINE-MODIFIED CELLULOSE NANOPARTICLES AS A CONTROLLED DELIVERY SYSTEM FOR THE ANTITUMORAL DRUG DOXORUBICIN

Abstract

This study explores the development and characterization of pH-responsive drug delivery systems (DDS), starting from the modification of cellulose polymer for targeting cancer therapy. Activated microcrystalline cellulose with Lithium Chloride in dimethylacetamide LiCl/DMAc system and chemically modified by various reagents was synthesized. Modification includes the synthesis of cellulose tosylate and dialdehyde cellulose (Cell-A) as primary intermediates, then by substitution, these intermediates were functionalized with moieties such as L-cysteine, melamine, p-phenylenediamine, and hydrazine, introducing thiol, amine, and imine groups on the cellulose backbone to produce stable and specialized drug carriers. FT-IR and NMR spectroscopies confirmed successful modifications. Cellulose-cysteine (Cell-Cys) nanoparticles loaded with quercetin were prepared with a diameter of 70–90 nm and a zeta potential of -28 mV, showing strong electrostatic stability. The quercetin loading efficiency on the nanoparticles reached about 17.04%. A significant pH-dependent behavior was shown by the release studies on different carriers for both quercetin and doxorubicin (DOXO), for example, the quercetin released from Cell-Cys was 70 times more at pH 6.5 (tumor pH) than at the physiological pH (7.4). Cell-A and cellulose-hydrazone showed accelerated release of doxorubicin in acidic conditions, caused by the protonation of functional groups and increased polymer swelling. Cytotoxicity assays demonstrated that DOXO released from Cell-A maintained remarkable potency against HepG-2 cells with an IC50 of 0.0089 µg/ml, nearly identical to the free drug (0.0088 µg/ml). These findings lead to the conclusion that modified cellulose nanocarriers offer a biocompatible, stable, and highly efficient platform for the controlled and triggered release of anticancer agents.