Nanotecnologia aplicada ao decoquinato para obtenção de novas terapias antimaláricas.

Abstract

Decoquinate (DQ) is a drug that has been investigated for its promising antiplasmodial activity against the erythrocytic and hepatic phases of the parasite in the search for an effective treatment for malaria in the various developmental stages of Plasmodium. However, DQ has a high lipophilicity that prevents its use in humans. The aim of this work was to review the literature on DQ, validate an analytical method for its quantification and solubility testing in the lipids and develop microemulsion (ME) and nanoemulsion systems (NE) to enable its use in humans. Validation experiments were performed by HPLC/DAD using a gradient mobile phase and a reversed phase column (C18) as stationary phase. The DQ stock solutions were prepared in methanol. The developed methodology was used for the solubility test in FO, where known amounts of DQ were added to different oil phases and stirred by sonication, the same method that was later used to develop the pseudoternary diagram and emulsified systems. From this diagram, based on the results of the solubility test, a formulation was reproduced, called ME-BCO, with the FO added with phosphatidylcholine to be described by transmission electron microscopy, dynamic light scattering (DLS), polydispersity index ( PdI) and zeta potential (PZ). ME-BCO was observed over a period of 90 days, evaluating macroscopic and physicochemical parameters. As a result, the improvement in solubility with the addition of the phospholipid in the tested oil phases was evident. Next, it is observed that DQ is quantifiable by a selective and precise method, in addition to the fact that the analytical methodology developed showed linearity (r2 = 0.9989), and detection and quantification limits of 3.33 and 11.09 μg /mL, respectively. The repeatability obtained indicates low variability. ME- BCO remained stable. The nanoemulsified system obtained by the diagram solubilized the drug, but needs optimization to circumvent the therapeutic inefficiency of DQ, and then be established as a new therapeutic alternative for malaria.