Design of docetaxel loaded polymeric nanoparticles, characterization, radiolabeled with 99mTc and in vitro evaluation

Recently the research into tumor-targeted diagnostic and therapeutic radiolabeled molecules or drugs is one of the potential areas of cancer drug development. There are several drug delivery systems such as liposomes, dendrimers, metallic and polymeric nanoparticles to improve targeted delivery of radiolabeled drugs to tumor site. In the present study, we have synthesized docetaxel (DTX) loaded polymeric nanoparticles (PLA-PEG) and radiolabeled with technetium-99m tricarbonyl core first time. The PLA-PEG nanoparticles were prepared by nanoprecipitation method. PLA-PEG nanoparticles were accomplished a result for structure characterization with Fourier Transform Infrared (FT-IR) spectroscopy and Nuclear Magnetic Resonance (H-NMR). Dynamic Light Scattering (DLS), Zeta Potantial Analysis and Scanning Electron Microscopy (SEM) imaging were applied to evaluate shape and surface morphology of synthesized PLA-PEG nanoparticles. The optimized formulation of DTX-loaded PLA-PEG nanoparticles had a particle size and polydispersity index of 120 ± 7,3 nm and −24,66 mV ± 1,5, respectively, which was further supported by SEM image. Radiochemical purity of DTX loaded PLA-PEG nanoparticles were determined by Thin Layer Radiochromatography (TLRC). The radiolabeling efficiency of docetaxel loaded PLA-PEG nanoparticles 99mTc(CO)3-PLA-PEG-DTX was found to be 95% ± 2,7. In vitro study was carried out on cancer lines ( MCF7, MDA-MD-231 breast cancer cell lines) to examine the biological behavior of docetaxel loaded PLA-PEG nanoparticles. It was specified that PLA-PEG-DTX complex was more toxic on MDA-MB-231 cell lines. Along with the research, while it was observed that 99mTc(CO)3-PLA-PEG-DTX complex had been decreased by time for MCF-7 cell lines, while uptake of MDA-MB-231 was stabilized up to 90 minutes and decreased at 120 and 240 minutes. Keywords: Docetaxel, polymeric nanoparticles, technetium tricarbonyl core, cell culture