Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL–PEG–PCL copolymeric-based micelles

Abstract

A reliable and efficient drug delivery system using PCL–PEG–PCL copolymers was established for the anti-cancer compound sulforaphane (SF) in this study. Encapsulated SF by PCL–PEG–PCL nanoparticles led to formation of SF-loaded PCL–PEG–PCL micelles. Micelles characterization and stability, the particle size and their morphology were determined by DLS and AFM. The loading efficiency of SF was 19.33 ± 1.28%. The results of AFM showed that the micelles had spherical shapes with the size of 107 nm. In vitro release of SF from SF-entrapped micelles was remarkably sustained. The cytotoxicity of free SF, PCL–PEG–PCL and SF/PCL–PEG–PCL micelles was analysis by MTT colorimetric assay on MCF-7, 4T1 and MCF10A cell lines. Expression levels of BCL-2, PARP, COX-2, Caspase-9 and ACTB genes were quantified by real-time PCR. Flow cytometry analysis was performed using the Annexin V-FITC Apoptosis Detection Kit to evaluate the apoptotic effects of free SF compared with SF/PCL–PEG–PCL micelles. Study of the in vivo pharmacokinetics of the SF-loaded micelles was carried out on SF-loaded PCL–PEG–PCL micelles in comparison with free SF. The results of in vivo experiments indicated that the SF loaded micelles significantly reduced the tumor size. In vivo results showed that the multiple injections of SF-loaded micelles could prolong the circulation period and increase the therapeutic efficacy of SF. Also, in comparison with the free-SF solution, encapsulation of the SF in micelles increased the mean residence time from 0.5 to 4 h and the area under the concentration–time curve up to 50 folds.