Pharmaceutical Sciences and Health Technologies IV.
Torma Lúcia
ELTE Analitikai Kémiai Tanszék
Lúcia Torma1
1: ELTE Analitikai Kémiai Tanszék
Introduction: Daunorubicin (DAU) is an anthracycline agent with an antitumour effect and is used in the treatment of different types of leukaemias. It is important to highlight the cardiotoxic properties of DAU, because this side effect can make the therapeutic use of it questionable. Albumin based nanoparticles are promising drug delivery systems (DDSs). Incorporating cytostatic agents into Bovine Serum Albumin Nanoparticles (BSA-NPs), their toxic properties can be reduced, the pharmacokinetic profile of drugs can be optimised and provide the opportunity to overcome multidrug resistance.
Aims: Our aims were to prepare DAU-incorporated BSA-NPs following the desolvation process (1); characterize the produced particles (2); optimize the preparation parameters (3); and examine the in vitro cytotoxic activity of prepared nanoparticles (4).
Methods: The general characterization of nanoparticles was determined by dynamic light scattering (DLS) and morphological investigation was performed on a Transmission Electron Microscope (TEM). The DAU-content of NPs was measured by a spectrofluorimetric calibration method. In vitro cytotoxic experiments were carried out using 4 different cell lines, and IC50 values of free drug and NPs treatment were determined by PrestoBlue cell viability assay.
Results: Different preparation parameters can influence the characteristics and therefore the cytotoxic properties of prepared nanoparticles. NPs prepared with the most ideal preparation parameters can be characterised as having a particle size of 180-200 nm, and an Encapsulation Efficiency (EE) of 65-70 %. All of the NPs showed cytotoxic effects on the tested cell lines. P388 cell line showed efficient cellular uptake of DAU and DAU-containing NPs after overnight incubation, and NPs could be characterised by sustained release in the tested media at 37 °C. NPs proved to be stable at 4 °C in different storage solutions for 8 weeks.
Based on these results, a standard protocol for the preparation of DAU-loaded BSA nanoparticles was elaborated. Furthermore, DAU-NPs were found to be able to reduce drug resistance.
Conclusion: Our findings provide the opportunity for further study, for instance testing the in vivo effect of NPs, or applying NPs containing daunorubicin and cytarabine in combinations in order to implement their synergistic effect.