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Amphotericin B (AmB) is a broad-spectrum antifungal drug used in the treatment of fungal invasive infections. However, its clinical use has been limited due to its side effects and toxicity, especially the nephrotoxicity. Furthermore, AmB presents low aqueous solubility, low permeability over the membranes and poor stability in the gastric environment, which makes it unavailable to be administered by the oral route. In this study, chitosan-coated poly (ε-caprolactone) nanoparticles were developed to provide the oral delivery of AmB and reduce its toxicity. Nanoparticles were obtained by nanoprecipitation and parameters as particle size, polydispersity index (PDI), zeta potential, morphology, in vitro AmB release (in physiological pH and simulated gastrointestinal fluids), state of molecular aggregation, cytotoxicity over erythrocytes and Vero cells line and in vitro antifungal activity were fully investigated. Nanoparticles presented mean size of 318 ± 35 nm, PDI of 0.24 ± 0.02, zeta potential of +36.2 ± 1.8 mV due to chitosan-coating, and 69% of AmB encapsulation. The kinetic release profile of AmB from nanoparticles was of second order and diffusion-governed in pH 7.4. The release in the gastrointestinal simulated fluids showed that the chitosan-coated PCL nanoparticles presented good stability during the time evaluated. AmB was released from nanoparticles in a state of low molecular aggregation. Cytotoxicity over erythrocytes and Vero cells line revealed that nanoencapsulation significantly reduced the AmB-related cytotoxicity (p < 0.05) compared to the free drug. In the antifungal activity against Candida parapsilosis strain, the MIC of AmB-loaded nanoparticles was 5-fold higher than free AmB, but the strain was susceptible to nanostructured AmB. Chitosan-functionalized PCL are potential carriers for the oral AmB delivery, reducing its cytotoxicity and maintaining its activity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: In this study, bovine serum albumin (BSA) nanoparticles coated with polysorbate- 80 (PS-80) and containing amphotericin B (AmB) were developed using a coacervation method., Methods: The nanoparticles were spherical, had a uniform size distribution (polydispersity < 0.25), a small mean size (185 ± 5 nm), a high zeta potential (-38.0 ± 0.7 mV), and a high AmB encapsulation efficiency (93 ± 1%). The AmB release profile was prolonged and diffusion-controlled, resulting in a low degree of AmB aggregation in solution. The physicochemical characteristics of these AmB containing nanoparticles were evaluated by X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and derivative thermogravimetry and showed that the nanoencapsulation process lead to AmB amorphization while maintaining its chemical integrity., Results: In a hemolysis assay, AmB-loaded PS-80-coated BSA nanoparticles demonstrated an absence of cytotoxicity toward erythrocytes, whereas pure and commercial AmB were highly hemolytic., Conclusion: In an assay to assess antifungal activity against Cryptococcus neoformans, AmB-charged PS-80-coated BSA nanoparticles were effective, however, due to the prolonged AmB release from the nanoparticles, the MIC was higher than for pure or commercial AmB. PS-80-coated BSA nanoparticles are potential carriers for the delivery of AmB for the treatment of Cryptococcus sp infections., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The antioxidant and anticandidal activities of leaves obtained from Camellia sinensis by non-fermentation (green and white teas), semi-fermentation (red tea) and fermentation method (black tea) were investigated. It was evaluated the total phenolic content by Folin-Ciocalteau assay; antioxidant capacities were evaluated in vitro using DPPH and ABTS radicals, hypochlorous acid and superoxide anion scavenger assays, induced hemolysis, lipid peroxidation by conjugated diene formation and myeloperoxidase activity. Anticandidal activity was performed on three strains of Candida spp. The results showed that non-fermented teas have a higher concentration of phenolic compounds, and then presented the best inhibitory activity of AAPH-induced hemolysis, the best inhibition of conjugated diene formation and more pronounced antioxidant activity in all tests. The highest anticandidal activity was obtained from fermented tea, followed by non-fermented tea. These results indicate that the antioxidant activity demonstrated has no direct relation with the anticandidal activity.

Apocynin (APO), curcumin (CUR) and vanillin (VAN) are o-methyl catechols widely studied due their antioxidant and antitumour properties. The effect of treatment with these o-methyl catechols on tamoxifen (TAM)-induced cytotoxicity in normal and tumour cells was studied. The cytotoxicity of TAM on red blood cells (RBC) was performed by haemoglobin or K(+)release and on polymorphonuclear leukocytes (PMNs) by trypan blue dye exclusion method. Cytotoxic activity was assessed in human chronic myeloid leukemia (K562) cell line by (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). According the release of haemoglobin and K(+), the CUR showed a decrease in TAM cytotoxicity on RBC; however, in PMN, APO, CUR and VAN showed increased of these cells viability. VAN presented the highest cytotoxicity on K562 cells, followed by APO and CUR. These results point the potential therapeutic value of these o-methyl catechols with TAM, particularly of CUR, which potentiates the cytotoxic effects of TAM on K562 cells and also decreases TAM-associated cytotoxicity on RBC and PMN.