Nanopartículas de PLA contendo derivado espiro-acridínico com atividade anticancerígena

Abstract

According to the World Health Organization (WHO), cancer is the second leading cause of death worldwide and accounted for 8.8 million deaths in the last year alone. Although chemotherapy is the most widely used therapy for cancer treatment, its efficacy depends on ensuring the delivery of the drug to the site of action and minimizing side effects. The spiro-acridine derivatives have demonstrated excellent antiproliferative activity in prostate and breast cancer tumor cell lines, but their high lipophilicity limits their use in the clinic. In the present work, the development and characterization of poly (lactic acid) polymer nanoparticles (PLA) had the objective of encapsulating the synthesized compound 3- (acridine-9-yl) -N-benzylidene-2-cyanoacrylhydrazide (AMTAC-01) to improve solubility and possible increase of drug delivery in the tumor tissue due to the effect of increased permeation and retention (EPR). The drug was obtained through a methodology already described in the literature and its structural verification demonstrated that the synthetic route followed is feasible even at larger scales than the one already reported. The nanoparticles were successfully obtained by the techniques of nanoprecipitation and simple emulsion (O / A). The mean particle size less than 200 nm and the low polydispersity index indicate that the proposed methods were satisfactory for nanoparticle production. The efficiency of incorporation of the drug into the nanoparticles revealed that the nanoprecipitation presented an encapsulation efficiency of 50.1% (± 0.22) and emulsification / evaporation by means of a simple emulsion (O / W) efficiency of 84.5% (± 0 , 14) showing that the encapsulation of the derivative in the nanoparticles is feasible. The negative zeta potential of the particles is a result of the carboxylic acid end chains of the polymer and is a strong indication of system stability. The analysis of atomic force microscopy (AFM) and scanning microscopy (SEM) showed the spherical and homogeneous profile of the nanoparticles and the in vitro release assay showed a sustained release of the drug by the Fickian diffusion mechanism. In vitro cytotoxicity studies in human umbilical cord cells (HUVEC) revealed toxicity dependent on the components of the formulation and concentration of the drug in the systems.