Desenvolvimento e avaliação in vitro de sistemas de liberação controlada de drogas para o tratamento da leishmaniose cutânea à base de nanofibran de PLA/PEO/ANPOTERICINA B produzidas por solution blow spinning (SBS)

Abstract

Cutaneous leishmaniasis (CL) is an infectious parasitic disease caused by the protozoan of the Leishmania genus, which promotes ulcers in exposed areas of the skin. Amphotericin B (AmB) is one of the drugs used in the treatment. However, its clinical use has limitations intravenously because of its high toxicity and low solubility, making it attractive to investigate vehicles for topical application as a safer way. Thus, in this work a nanostructured topical drug delivery system (TDDS) was proposed using the solution blow spinning (SBS) technique. Fibers of blends of poly(ethylene oxide), PEO, and poly(lactic acid), PLA, with and without AmB were produced by SBS. PEO/PLA fibers in two different weight ratios 50:50 and 70:30, with 0, 0.25, and 1.0% AmB were produced in the form of mats that were morphologically characterized by scanning electron microscopy ( SEM), thermally by thermogravimetry (TG) and differential scanning calorimetry (DSC) and microstructurally by Fourier transform infrared spectroscopy (FTIR) and the degree of hydrophobicity of its surface was verified through the contact angle. The determination of the AmB release profile, the efficiency of incorporation and the drug load were evaluated by spectroscopy (UV-Vis). The degree of swelling of the samples was determined. The release curves were fitted by kinetic models to provide crucial information about the function of the material systems that constitute them. In vitro assays of leishmanicidal activity were determined in promastigote forms of Leishmania amazonensis. The results show that the systems produced by SBS consist of rough fibers for all compositions. AmB was incorporated into the nanofibers and the materials were shown to be thermally stable within the physiological temperature range. The significant increase in drug incorporation occurred in structures with higher proportions of PLA, which has hydrophobic character, higher contact angles, however, the maximum controlled release (88%) after 14 days was found in samples with higher proportions of PEO and AmB . The Peppas-Sahlin model showed the best mathematical fit (R2 ≥ 0.95). The 50:50 samples showed non-Fickian transport, indicative of the combination of drug diffusion mechanisms and polymeric erosion. On the other hand, dressings with higher proportions of PEO showed the Fickian diffusion mechanism, in addition to higher degrees of swelling. All the nanostructured topical drug delivery system with AmB showed leismanicidal activity within 72 h, the highest activities were found for samples with 1.00% of the drug. The results obtained suggest that TDDS control the availability of AmB and have leishmanicidal activity with potential to be used in the local treatment of CL.