Exosome-loaded Paclitaxel: Preparation and toxicity evaluation on two glioblastoma cell lines

Abstract

Objective(s): Exosomes are endogenous nanovesicles act as intercellular communication tools which have been considered to utilize as drug delivery systems. As transporting therapeutic molecules into brain has obstacles, preparing exosomes which have the potential to pass through its barriers is great challenge. Methods: Exosomes isolated from cell culture media of U87 glioblastoma cells were characterized. In the next step, paclitaxel (PTX) was loaded into them to investigate the cytotoxicity of this formulation on two cell line of glioblastoma, U87 and T98G. Pharmaceutical characterizations such as size analysis, PTX encapsulation efficiency and FESEM/TEM imaging of exosomes were also evaluated. Results: CD9 as a biomarker of exosomes was detected in extracted samples to confirm the presence of exosomes.Size analysis and electron microscopy imaging proved nano-range of isolated and drug loaded exosomes. The cytotoxicity of empty exosomes of U87 cells was different on U87 and T98 cells. Exosomes diminished cell viability in U87 cells compared with control group while in T98 cell line they didn’t have any effect on cell viability after 24 or 48 h time intervals. The cytotoxicity of drug loaded exosomes was different at two time intervals where PTX loaded exosomes had no effect or 30 % cell viability decrease on T98 cells after 24 and 48 h, respectively. Conclusions: Increased cytotoxicity of PTX after entrapment into exosomes and BBB transport capability of exosomes promises an appropriate brain drug delivery system for in vivo characterization in GBM animal model.