RESUMEN
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.
Asunto(s)
Cilostazol/administración & dosificación , Preparaciones de Acción Retardada/química , Nanofibras/química , Poliésteres/química , Rastreo Diferencial de Calorimetría , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
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.