Exploratory Study on the Effects of Biodegradable Nanoparticles with Drugs on Malignant B Cells and on a Human/Mouse Model of Burkitt Lymphoma

Gustavo      H. Marin; Eduardo      Mansilla; Nelly      Mezzaroba; Sonia      Zorzet; Luis      Nunez; Gustavo      Larsen; Jose      M. Tau; Alberto      Maceira; Ruben      Spretz; Carol      Mertz; Sabrina      Ingrao; Claudio      Tripodo; Francesco      Tedesco; Paolo      Macor

Abstract

The aim of this study was to determine if Rituximab coated Biodegradable Nanoparticles (BNPs) loaded with Chlorambucil and Hydroxychloroquine could induce apoptosis of B-Chronic Lymphocytic Leukemia (B-CLL), MEC-1 and BJAB cells in vitro and evaluate their toxic and therapeutic effects on a Human/Mouse Model of Burkitt Lymphoma at an exploratory, proof of concept scale. We found that Rituximab-Chlorambucil-Hydroxychloroquine BNPs induce a decrease in cell viability of malignant B cells in a dose-dependent manner. The mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the B-CLL cells after Annexin V/propidium iodide staining. Additional data revealed that these BNPs were non toxic for healthy animals, and had prolonged survival in this mice model of human lymphoma.

Keywords: B cells, CLL, lymphoma, nanoparticles, chlorambucil, hydroxychloroquine, rituximab.

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