In vitro cell interaction and in vivo biodistribution of poly (dl-lactide-co-glycolide) nanospheres with encapsulated selenium nanoparticles for the treatment of liver diseases

Abstract

The role of selenium as a chemopreventive and chemotherapeutic agent has been supported by a large number of epidemiological, preclinical, and clinical trials [1, 2] suggesting that anti-tumor effect mechanisms of selenium include induction of apoptosis, inhibition of cell proliferation, protection against oxidative stress, and stimulation of immune system. Herein we demonstrate a simple and quick synthesis of uniform, stable, amorphous selenium nanoparticles (SeNps), using ascorbic acid as the reduction agent. The choice of an appropriate stabilizer and reducing agent for preparation of stable selenium nanoparticles is very important. We used bovine serum albumin (BSA) as an organic layer for selenium nanoparticles, i.e., as a capping agent to make them more biocompatibile and protect them from agglomeration in the suspension medium. SeNps were additionally encapsulated within spherical PLGA particles (PLGA/SeNps). One of the most important requirements for the controlled and balanced release of the drug in the body is ideal spherical shape of the particles and narrow distribution of their sizes. The morphology (size and shape) of the particles plays key role in their adhesion and interaction with the cell. The influence of PLGA/SeNps on cell viability, ROS generation in HepG2 cells, as well as anticancer activity against epithelial tumor cells was investigated. Synthesized nanoparticles were characterized by FTIR spectroscopy, FESEM, TEM, HRTEM, and Zeta potential measurements. As a part of this study, we have also performed in vivo dynamic imaging studies in normal mice, using SPECT imaging and a high resolution gamma camera. The PLGA/SeNps nanoparticles have been radiolabelled with Tc-99m, by applying the direct labeling method [3]. Ex vivo biodistribution measurements, as well as in vivo dynamic studies up to 1h p.i. and at 24h were performed, showing increased concentration in liver and spleen.

Acknowledgements This study was supported by the Ministry of Science and Technological Development of the Republic of Serbia, under Grant No. III45004: Molecular designing of nanoparticles with controlled morphological and physicochemical characteristics and functional materials based on them. Presented were the results of a study also supported by the COST Action TD1004.

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