Preparation and pharmacokinetics of bifunctional epirubicin-loaded micelles.

Abstract

In this study, micelles were designed to deliver an antitumor agent and a fluorescent marker to a tumor site. The micelles simultaneously encapsulated epirubicin (EPI) and polyethylene glycol (PEG)-modified graphene quantum dots (GQDs-PEG), and employed a PEG-polylactic acid block copolymer amphiphilic block polymer as a nanocarrier. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the functional groups in the synthesized GQDs-PEG. A Malvern particle size meter and transmission electron microscopy were used to show that the particle size of the GQDs-PEG is approximately 2-9 nm, and that of the bifunctional EPI-loaded micelles (EPI-FIDCR) is 19.59±1.21 nm, with zeta potential at -22.87±0.85 mV. The EE% and DL% for EPI in EPI-FIDCR are 74.02±0.55 % and 3.78±0.28 %, respectively. The IC50 values of EPI-FIDCR and EPI solution (EPI-Free) for tumor cells were 7.03 μg/mL and 5.54 μg/mL, showing that EPI-FIDCR still maintained strong cytotoxicity. Fluorescence micrographs of HeLa cells incubated with GQDs-PEG and EPI-FIDCR for 6 h, respectively, show that only EPI-FIDCR could enter the cells. In vitro cellular uptake assays and an inhibition study indicated that EPI-FIDCR could deliver both EPI and GQDs-PEG into tumor cells, while maintaining an inhibitory effect similar to that of unencapsulated EPI. A pharmacokinetic study showed that EPI-FIDCR could persist in the circulation for a significant period of time. The AUC0→t calculated for the EPI-FIDCR formulation was 159.5-fold compared with that of EPI-Free, based on its improved stability and prolonged blood circulation time. The EPI-FIDCR enables both fluorescence imaging and controlled drug-release, exhibits prolonged systematic circulation time and has potential for the treatment of cancer.