Formulation development and in vitro–in vivo anticancer potential of novel nanoliposomal fluorinated curcuminoids

Abstract

Curcumin (CUR) has proven efficacy in a wide range of medical conditions; however, due to its poor water solubility its therapeutic application has been restricted. Difluorintaed Curcumin (CDF), a curcumin analog with enhanced anticancer activity, has recently been reported. Here, fluorinated derivatives of CUR and desmthoxycurcumin (DMC) were synthesized, and nanoliposomal formulations developed. Results showed that the entrapment efficiency of nanoliposomal fluorinated CUR and fluorinated DMC as 78 % and 95 %, respectively. In the cancer cell lines, we showed that liposomal fluorinated CUR and liposomal fluorinated DMC inhibited cellular proliferation at micromolar concentrations (0.5–0.9 M). In vivo studies conducted in female BALB/c mice demonstrated further that both liposomal fluorinated derivatives greatly limit tumor development when compared to LCUR. Additionally, in combination therapy, liposomal fluorinated CUR or DMC mixed with liposomal doxorubicin (PLD) improved the time to reach endpoint (TTE) percentage tumor growth delay (TGD %), median survival time (MST) and percentage increase in lifespan (ILS %) values compared to doxorubicin formulation alone (P < 0.05). TTE values for LCUR, LF, LDF, and PBS were 32.9 ± 2.4, 41.7 ± 2.1, 39.0 ± 2.0, and 28.5 ± 2.0 days, respectively. In summary, the synthesized fluorinated curcumin analogs inhibit cancer cell proliferation to a greater extent than curcumin; thus, demonstrate excellent potential in cancer therapy.