PLGA-Nanoparticles loaded with a thiosemicarbazone derived palladium (II) complex as a Potential Agent to New Formulations for human ovarian carcinoma treatment

The complex named triphenylphosphane-chlorido(pyrenecarboxaldehyde-N(3)-cyclohexyl-thiosemicarbazonate)palladium(II), [PdCl(PPh3)(PrCh)], has been recently selected as a promising cytotoxic agent against resistant ovarian cancer cells, by inhibiting the topoisomerase IB enzyme. In order to increase the efficacy of this promising drug, in the present work the influence of the encapsulation process of PdII complex into poly(lactic-co-glycolic acid) (PLGA) polymer was studied. The PLGA nanoparticles containing the PdII complex (NPs-PLGA-PdII) were prepared by using an emulsion-solvent evaporation technique and fully characterized by using DLS and SEM. The results showed that the PLGA-NPs containing the PdII complex can be obtained successfully through an emulsion-solvent evaporation method with a high encapsulation efficiency (96 %). Furthermore, the PLGA-NPs revealed to be suitable as a controlled release carrier system for [PdCl(PPh3)(PrCh)], since in vitro tests displayed a slow and sustained release of the PdII complex. After the PdII encapsulation on the PLGA-NPs, biological studies were assayed by using the OVCAR3 cell line (human ovarian carcinoma cells). The study of cytotoxicity by resazurin assay showed that the formulation led to a significant reduction of the ovarian cell viability (80 % at 1 μM) more than the non-encapsulated complex or cisplatin. Most notably, it must be highlighted the relevant cytotoxicity of the Nano-PLGA-PdII against cisplatin resistant cell line used in this work since resistance is one of the major challenges for chemotherapy.