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Complementing to our previous studies in biopolymers and amino acids for medical applications this study was addressed to design a unique therapeutic regime consisting of a cocktail from therapy with amino acids (TAAI) and polymer therapy for cancer disease. This regime is depending on synthesized Doxorubicin loaded chitosan-glutamic acid (Cs-Ga-DOX) nanoparticles via ionic gelation pathway. The encapsulation efficiency was 69%. The average size was 20-37 nm with spherical, homogenous structure, and positive zeta potential. FTIR of Cs-Ga confirmed the formation of amide linkage at 1644 cm-1. The in-vitro release of DOX was examined for both pH 5.5 and 7.4 to be biphasic with mutual burst release followed by sustained release for 168 h to reach 58% at pH 5.5 and 25% at pH 7.4. This result suggested that Cs-Ga nanoparticles presented a promising mixture of glutamic amino acid and chitosan as pH-responsive nano-carrier for anticancer drugs.

In this study, Superparamagnetic magnetite nanoparticles (SPMNPs) are used in a new way as direct nanocarrier for Doxorubicin hydrochloride (DOX) via the functionalization of their surface with tri-sodium citrate through ligand exchange to conjugate DOX with imine bond to form tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (DOX/Cit-MNPs). The DOX/Cit-MNPs were coated with chitosan to form chitosan coated citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) to offer biodegradability and pH-sensitive drug release features. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed functionalization of SPMNPs, DOX-conjugation, and chitosan coating. The trans electron microscopy (TEM) show spherical nanostructures with average size 40 nm for coated nanocarriers. The saturation magnetization value of carrier was 59 emu/g.The in-vitro release of DOX from the chitosan coated tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) was studied to be 75% at pH 5.5 and 28.6% at pH 7.4 which proves the pH sensitivity of encapsulated Cs/DOX/Cit-MNPs. The effect of Cs/DOX/Cit-MNPs toward Human Breast Cancer Cell lines (MCF7) was studied and found to be 76% without magnet and 98% with external magnet after 72 h. With increasing DOX concentration and treatment time, the cell inhibition (IR%) of DOX solution and Cs/DOX-Cit-MNPs suspension to all cells is increased. Cs/DOX/Cit-MNPs showed sustained release and good inhibition to cancer cells and offer a protective mode for normal cells (WISH) compared to the free DOX. Graphical Abstract