RESUMO
The therapeutic administration of cytokines has been introduced aiming to modulate the immune response system, seeking for different approaches to face pathologies such as cancer, auto immune and infectious diseases. The objective of this study was to investigate the effects of a stable oil-in-water (O/W) nanoemulsion system carrying the cytokine Interferon gamma (IFN-γ) on the activity of phagocytes and MCF-7 human breast cancer cells. Nanoemulsions were prepared through ultra-homogenization, and they consisted of distilled water, triglycerides of capric acid/caprylic, sorbitan-oleate, polysorbate 80, and 1-butanol. IFN-γ (100 ng ml-1 ) was incorporated into two O/W nanoemulsion formulations, and these formulations were characterized in terms of their preliminary and accelerated physicochemical stability, rheological properties, droplet size, polydispersity and surface charge. We identified the most optimal IFN-γ nanoemulsion (IFN-γNE2), which remained stable under extreme temperature variations for 90 days, contained an average dose of 97 ng ml-1 of IFN-γ and exhibited a biocompatible pH and a relative stable rheological profile. Cell viability and intracellular Ca2+ release assays conducted showed that IFN-γNE2 reduced the cell viability of MCF-7 cells without affecting the cell viability of phagocytes. Furthermore, IFN-γNE2 was able to induce cellular activity of phagocytes as evidenced by increased intracellular Ca2+ release in these cells. Our findings on this IFN-γ nanoemulsion suggest that it can be a promising therapeutic agent for immunostimulation and cancer treatment.
Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Emulsões/química , Fatores Imunológicos/administração & dosagem , Interferon gama/administração & dosagem , Adulto , Antineoplásicos/farmacologia , Células Cultivadas , Feminino , Humanos , Fatores Imunológicos/farmacologia , Interferon gama/farmacologia , Células MCF-7 , Masculino , Neoplasias/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: The adipose tissue has been recognized as an important endocrine organ, which is metabolically active and expresses and secretes various inflammatory cytokines. Inflammation is involved in obesity-related complications. As such, the present study investigated the correlation between biochemical parameters, serum proinflammatory cytokines and adipokines in individuals with obesity. METHODS: Based on the body mass index (BMI), 30 subjects were divided into 3 groups: eutrophic (GC, n = 10), overweight (GOW, n = 10) and obese (GOB, n = 10). Serum glucose, cholesterol (total-C, HDLC and LDL-C), triglycerides, total proteins, uric acid and insulin were determined, as well as cytokines IL-8, TNF-α, IL-1ß, and IL-6, leptin and adiponectin. RESULTS: GOB showed the highest glucose, total and LDL-C, triglycerides, uric acid, insulin, leptin, IL- 8, IL-1ß, IL-6, TNF-α and lowest adiponectin levels. In general, adiponectin exhibited an inverse correlation with BMI, abdominal circumference, LDL-C, IL-6, TNF-α, leptin and leptin-adiponectin ratio (LAR) and a positive correlation with HDL-C. Leptin was positively correlated with BMI, abdominal circumference, insulin, IL-6, TNF-α and LAR and negatively correlated with HDL-C and adiponectin. The LAR was positively correlated with BMI, waist circumference, insulin, TNF-α and negatively associated with HDL-C. CONCLUSION: The results confirm that obesity changes the lipid and glycemic profiles of individuals, increases the proinflammatory adipokine levels and reduces those of anti-inflammatory adipokines, promoting a state of chronic inflammation.