RESUMEN
Artemether (ATM) cardiotoxicity, its short half-life and low oral bioavailability are the major limiting factors for its use to treat malaria. The purposes of this work were to study free-ATM and ATM-loaded poly-ε-caprolactone nanocapules (ATM-NC) cardiotoxicity and oral efficacy on Plasmodium berghei-infected mice. ATM-NC was obtained by interfacial polymer deposition and ATM was associated with polymeric NC oily core. For cardiotoxicity evaluation, male black C57BL6 uninfected or P. berghei-infected mice received, by oral route twice daily/4 days, vehicle (sorbitol/carboxymethylcellulose), blank-NC, free-ATM or ATM-NC at doses 40, 80 or 120 mg kg-1. Electrocardiogram (ECG) lead II signal was obtained before and after treatment. For ATM efficacy evaluation, female P. berghei-infected mice were treated the same way. ATM-NC improved antimalarial in vivo efficacy and reduced mice mortality. Free-ATM induced significantly QT and QTc intervals prolongation. ATM-NC (120 mg kg-1) given to uninfected mice reduced QT and QTc intervals prolongation 34 and 30%, respectively, compared with free-ATM. ATM-NC given to infected mice also reduced QT and QTc intervals prolongation, 28 and 27%, respectively. For the first time, the study showed a nanocarrier reducing cardiotoxicity of ATM given by oral route and it was more effective against P. berghei than free-ATM as monotherapy.
Asunto(s)
Antimaláricos/administración & dosificación , Arteméter/administración & dosificación , Cardiotoxicidad/prevención & control , Nanocápsulas/química , Plasmodium berghei/efectos de los fármacos , Administración Oral , Animales , Antimaláricos/toxicidad , Arteméter/toxicidad , Modelos Animales de Enfermedad , Electrocardiografía , Femenino , Malaria/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Drug delivery devices are attractive alternatives to drugs usually orally administrated. Therefore, this work aimed to produce PLA/PBAT-based nanofibers for the controlled release of cilostazol, evaluating the effect of different drug concentrations (20 and 30%) over the properties of the fibers. The fibers were characterized by scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), x-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric (TG/DTG), and mechanical analysis. SEM results indicated a high concentration of drug crystals on the surface of the fibers that contained 20% of cilostazol. These fibers were also thinner, more crystalline, less thermally stable, and less fragile in comparison to the fibers containing 30% of cilostazol, according to the XRD, DSC, TG/DTG, and mechanical results. The controlled release assays indicated that the fibers containing 20% of cilostazol would be attractive for short-term releases, reaching the equilibrium after approximately 6 h, while the ones containing 30% would ensure a slower release (~ 12 h). Despite the differences, both fibers would improve and enhance the efficiency of the treatment, and they would also prevent possible side effects caused by the drug to the gastric system.