Folate-targeted nanomicelles containing silibinin as an active drug delivery system for liver cancer therapy

The majority of herbal anticancer drugs are insoluble in water or become unstable during their transport to tumor tissues, hence they require a special drug delivery system. The main target of this study was to evaluate the therapeutic efficacy of silibinin (SLB)-loaded folic acid (FA)-conjugated Pluronic F127 (SLB-F127-FA) nanomicelles as an active-targeted drug delivery platform for liver cancer treatment. To prepare SLB-F127-FA nanomicelles, folic acid was first conjugated to hydrophilic chains of Pluronic F127 copolymer by the Steglich esterification technique. Then, silibinin was encapsulated in the self-assembled hydrophobic core of FA-conjugated F127 to render SLB-F127-FA nanomicelles. The prepared nano micelles had an almost spherical shape with an average particle size of 17.7 nm. The average hydrodynamic size of non-targeted (SLB-F127) and targeted (SLB-F127-FA) nanomicelles, measured by dynamic light scattering analysis (DLS), was 19.6 and 29.2 nm, respectively. Also, the drug loading content as well as entrapment efficiency of SLB-F127-FA nanomicelles were obtained to be 2.36% and 79.43%, respectively. The in vitro release patterns of SLB from nanomicelles showed a slow and sustained release behavior in comparison to free SLB. Moreover, it was observed that the kinetic release of silibinin from the SLB-F127-FA nanomicelles at 37 °C conforms well to Korsmeyer-Peppas kinetic model (R 2 = 0.99, n = 0.22), suggesting a dominate release mechanism of the Fickian diffusion type. Moreover, in vitro cytotoxic study indicated that the viability of human liver cancer cells (HepG2) exposed to SLB-PF127-FA nanomicelles was significantly lower than that of treated with non-targeted nanomicelles (SLB-F127) or free SLB. Our results suggest that SLB-F127-FA nanomicelles can be considered as a promising targeted drug delivery platform for liver cancer therapy and/or delivering other hydrophobic drugs to different types of cancers with folate-receptor overexpression.