Formulations of highly antiproliferative hydrophobic Pt(IV) complexes into lipidic nanoemulsions as delivery vehicles

The two Pt(IV) complexes (OC-6–33)-(cyclohexane-1R,2R-diamine)dichloridodiheptanoatoplatinum(IV) (1) and (OC-6–33)-(cyclohexane-1R,2R-diamine)dichloridodioctanoatoplatinum(IV) (2) were formulated with Intralipid® (IL) as a proof-of-concept to evaluate the delivery of lipophilic metal compounds to cancer cells. Negatively charged nanoemulsions ranging from 287 to 312 nm were obtained. The IL formulations show an increase in cancer cell accumulation (A2780 ovarian cancer cells) by a factor 6–7 with respect to the free complexes. In spite of the expected antiproliferative properties, in the cytotoxicity experiments free complexes showed values of the half-maximal inhibitory concentration (IC₅₀) from 2 to 6 times lower with respect to the IL formulations. However, the presence of IL was not totally detrimental of the potency, that is still in the nanomolar range, and, hence, a possible use in vivo, should not be excluded a priori.