Mucoadhesive nanoemulsion enhances brain bioavailability of luteolin after intranasal administration and induces apoptosis to SH-SY5Y neuroblastoma cells.

Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children and accounts for 7 % of all childhood malignancies and 15 % cancer mortality in children. Luteolin (LUT) is recognized by its anticancer activity against several types of cancer. The aim of this study was to prepare chitosan-coated nanoemulsion containing luteolin (NECh-LUT), investigate its potential for brain delivery following intranasal administration, and to evaluate its cytotoxicity against neuroblastoma cells. NECh-LUT was developed by cavitation process and characterized for its size, surface charge, encapsulation efficiency, and mucoadhesion. The developed formulation presented size 68 ± 1 nm, zeta potential + 13 ± 1 mV, and encapsulation efficiency of 85.5 ± 0.3 %. The NECh-LUT presented nearly 6-fold higher permeation through the nasal mucosa ex vivo and prolonged LUT release up to 72 h in vitro, following Baker-Lonsdale kinetic model. The pharmacokinetic evaluation of NECh-LUT revealed a 10-fold increase in drug half-life and a 4.4 times enhancement in LUT biodistribution in brain tissue after intranasal administration of single-dose. In addition, NECh-LUT inhibited the growth of neuroblastoma cells after 24, 48 and 72 h in concentrations starting from 2 µM. The NECh-LUT developed for intranasal administration proved to be a promising alternative for brain delivery of LUT, and a viable option for the treatment of neuroblastoma.

Imbalanced testicular metabolism induced by thyroid disorders: New evidences from quantitative proteome.

Thyroid dysfunctions, such as hypothyroidism and hyperthyroidism, are the second most prevalent endocrinopathies and are associated to reproductive disorders in men. Several genes are differentially modulated by thyroid hormones in testes and imbalances in thyroid hormone levels are also associated to alterations on sperm functionality. Imbalances on antioxidant defense mechanism and stress oxidative have been pointed out as the main factors for the impairments on male reproductive function. To clarify this issue, we investigated the expression and activity of antioxidant enzymes in testis, followed by their proteomic profile in attempt to characterize the mechanisms involved in the alterations induced by hypo- or hyperthyroidism in adult male rats. Hypothyroidism reduced the Gsr transcript expression and the activity of CAT and GSR enzymes, while the hyperthyroidism reduced the Gpx4 var2 transcript expression. Among 1082 identified proteins, 123 and 37 proteins were downregulated by hypothyroidism compared to euthyroid and hyperthyroid condition, respectively, being 36 proteins commonly reduced in both comparisons and one exclusively in hypo-hyperthyroidism comparison. A network containing 29 nodes and 68 edges was obtained in protein-protein interaction analysis and the functional enrichment analysis of differentially expressed proteins revealed significant alterations for several functions in hypo-euthyroid and hypo-hyperthyroid comparisons, such as ATP metabolic process, coenzyme binding, sperm part, peroxiredoxin activity, mitochondrial protein complex, intramolecular oxidoreductase activity, binding of sperm to zona pellucida, glutathione transferase activity, response to testosterone. Thus, there is a correlation between thyroid disorders and impaired antioxidant defense mechanism, resulting in reproductive dysfunctions, as infertility, mainly observed in hypothyroidism.