Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity.

ABSTRACT

Block copolymer micelles (BCMs) can be used to improve the solubility of lipophilic drugs and increase their circulation half-life. Hence, BCMs assembled from MePEG-b-PCL were evaluated as drug delivery systems of gold(III) bis(dithiolene) complexes (herein AuS and AuSe) to be employed as antiplasmodial drugs. These complexes exhibited remarkable antiplasmodial activity against liver stages of the Plasmodiumberghei parasite, and low toxicity in a model of zebrafish embryos. To improve the complexes' solubility, BCMs were loaded with AuS, AuSe, and the reference drug primaquine (PQ). PQ-BCMs (Dh = 50.9 ± 2.8 nm), AuSe-BCMs (Dh = 87.1 ± 9.7 nm), and AuS-BCMs (Dh = 72.8 ± 3.1 nm) were obtained with a loading efficiency of 82.5%, 55.5%, and 77.4%, respectively. HPLC analysis and UV-Vis spectrophotometry showed that the compounds did not suffer degradation after encapsulation in BCMs. In vitro release studies suggest that AuS/AuSe-BCMs present a more controlled release compared with PQ-loaded BCMs. The antiplasmodial hepatic activity of the drugs was assessed in vitro and results indicate that both complexes present higher inhibitory activity than PQ, although encapsulated AuS and AuSe presented lower activity than their non-encapsulated counterparts. Nevertheless, these results suggest that the use of BCMs as delivery vehicles for lipophilic metallodrugs, particularly AuS and AuSe, could enable the controlled release of complexes and improve their biocompatibility, constituting a promising alternative to conventional antimalarial treatments.