Lipoprotein Based Targeted Therapy for Acute Myelogenous Leukemia

Date

2020

Authors

Sabnis, Nirupama
Kvinta, Ryan
Lacko, Andras G.
Saranya Conjeevaram Nagarajan, Bhavani
Dossou, Akpedie
Raut, Sangram
Ahmed, Nadia

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Abstract

Purpose: The purpose of this project was to initiate studies to develop nano-formulations for anti-cancer agents to treat Acute Myeloid Leukemia (AML) via enhancing their targeting efficiency, cytotoxicity and reducing off-target toxicities. Methods: A computer optimized formulation of rHDL-Valrubicin was characterized for its physical and chemical properties. The diameter of the nanoparticles and the zeta potential were measured by Malvern Zetasizer. The anisotropy was measured by Cary eclipse spectrofluometer. The drug entrapment efficiency was measured by absorbance of valrubicin at 490nm. The cytotoxicity of the formulation was tested in 2 Leukemia cell lines, Kasumi-1 and AML-193, using cell counting kit 8, Dojindo Molecular Technologies. The cardioprotective effect of the formulation was investigated in Rat cardiomyocytes cells, (H9C2). Results: rHDL-Valrubicin formulations were successfully prepared with drug entrapment efficiency of 31.8%. The formulation was non leaky and homogeneous with average particle diameter of the 13.2 ± 2.2 nm and the average zeta potential was found to be -2.39 ± 9.81 mV. The rHDL-Valrubicin formulation exhibited 50 times more cardioprotective effect as compared to free valrubicin. In the Leukemia cell lines Kasumi-1 and AML-193, the inhibitory concentration required to kill 50% of cells (IC50) using the rHDL-Valrubicin formulation was observed to be 1.5 and 1.9 times more effective than the free valrubicin respectively. Conclusion: These proof of concept studies indicate the potential of rHDL as a drug delivery platform to mitigate the cardiotoxicity associated with anthracycline use in the treatment of AML.

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