Avaliação das atividades antioxidante, anticoagulante e antiproliferativa de extratos aquosos de marsdenia megalantha

The species of the genus Marsdenia, Apocynaceae, are widely used in folk medicine of several countries. In Brazil is found several species belonging to this genus. The in vitro antioxidant, anticoagulant and antiproliferative activities were evaluated to aqueous extracts of stalk, leaf and root of Marsdenia megalantha. In the total antioxidant capacity assay (expressed as ascorbic acid equivalents) the stalk extract showed 76.0 mg/g, while leaf and root extracts 141.3 mg/g and 57.0 mg/g, respectively. The stalk and leaf extracts showed chelating activity around 40% at 1.5 mg/mL, while root extract, at the same concentration showed, 17%. Only the leaf extract showed a significant ability in superoxide scavenging (80% at 0.8 mg/mL). Any extract was able in scavenge hydroxyl, as well anticoagulant activity. The antiproliferative activity of the extracts was evaluated against HeLa tumor cell line. The extracts inhibited in a dose-dependent manner the cell growth. However, the leaf extract showed 80% of inhibition at 1.0 mg/mL, while stalk and root extracts inhibited 63% and 30%, respectively. To assess the mechanism of cell death caused by the leaf extract in HeLa, was performed flow cytometry and western blot. The results show that leaf extract induces cell death by apoptosis through an activation caspase-independent pathway. These data indicate that stalk and leaf extracts obtained have potential to be used as antioxidants and anticancer drugs

O direito à saúde e a política nacional de atenção oncológica: uma análise a partir da crescente judicialização dos medicamentos antineoplásicos

The 1988 Federal Constitution of Brazil by presenting the catalog of fundamental rights and guarantees (Title II) provides expressly that such rights reach the social, economic and cultural rights (art. 6 of CF/88) as a means not only to ratify the civil and political rights, but also to make them effective and practical in the life of the Brazilian people, particularly in the prediction of immediate application of those rights and guarantees. In this sense, health goes through condition of universal right and duty of the State, which should be guaranteed by social and economic policies aimed at reducing the risk of disease and other hazards, in addition to ensuring universal and equal access to actions and services for its promotion, protection and recovery (Article 196 by CF/88). Achieving the purposes aimed by the constituent to the area of health is the great challenge that requires the Health System and its managers. To this end, several policies have been structured in an attempt to establish actions and services for the promotion, protection and rehabilitation of diseases and disorders to health. In the mid-90s, in order to meet the guidelines and principles established by the SUS, it was established the Política Nacional de Atenção Oncológica PNAO, in an attempt to sketch out a public policy that sought to achieve maximum efficiency and to be able to give answers integral to effective care for patients with cancer, with emphasis on prevention, early detection, diagnosis, treatment, rehabilitation and palliative care. However, many lawsuits have been proposed with applications for anticancer drugs. These actions have become very complex, both in the procedural aspects and in all material ones, especially due to the highcost drugs more requested these demands, as well as need to be buoyed by the scientific evidence of these drugs in relation to proposed treatments. The jurisprudence in this area, although the orientations as outlined by the Parliament of Supreme Court is still in the process of construction, this study is thus placed in the perspective of contributing to the effective and efficient adjudication in these actions, with focus on achieving the fundamental social rights. Given this scenario and using research explanatory literature and documents were examined 108 lawsuits pending in the Federal Court in Rio Grande do Norte, trying to identify the organs of the Judiciary behave in the face of lawsuits that seeking oncology drugs (or antineoplastic), seeking to reconcile the principles and constitutional laws and infra constitutional involving the theme in an attempt to contribute to a rationalization of this judicial practice. Finally, considering the Rational Use of health demands and the idea of belonging to the Brazilian people SUS, it is concluded that the judicial power requires ballast parameters of their decisions on evidence-based medicine, aligning these decisions housing constitutional principles that the right to health and the scientific conclusions of efficacy, effectiveness and efficiency in oncology drugs, when compared to the treatments offered by SUS

Avaliação das atividades antioxidante, anticoagulante e antiproliferativa de extratos aquosos de marsdenia megalantha

The species of the genus Marsdenia, Apocynaceae, are widely used in folk medicine of several countries. In Brazil is found several species belonging to this genus. The in vitro antioxidant, anticoagulant and antiproliferative activities were evaluated to aqueous extracts of stalk, leaf and root of Marsdenia megalantha. In the total antioxidant capacity assay (expressed as ascorbic acid equivalents) the stalk extract showed 76.0 mg/g, while leaf and root extracts 141.3 mg/g and 57.0 mg/g, respectively. The stalk and leaf extracts showed chelating activity around 40% at 1.5 mg/mL, while root extract, at the same concentration showed, 17%. Only the leaf extract showed a significant ability in superoxide scavenging (80% at 0.8 mg/mL). Any extract was able in scavenge hydroxyl, as well anticoagulant activity. The antiproliferative activity of the extracts was evaluated against HeLa tumor cell line. The extracts inhibited in a dose-dependent manner the cell growth. However, the leaf extract showed 80% of inhibition at 1.0 mg/mL, while stalk and root extracts inhibited 63% and 30%, respectively. To assess the mechanism of cell death caused by the leaf extract in HeLa, was performed flow cytometry and western blot. The results show that leaf extract induces cell death by apoptosis through an activation caspase-independent pathway. These data indicate that stalk and leaf extracts obtained have potential to be used as antioxidants and anticancer drugs

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Nanopartíulas de magnetita com oxacilina obtida por moagem de alta energia para aplicações biomédicas

The drug targeting has been the subject of extensive studies in order to develop site-specific treatments that minimize side effects and become more effective anticancer therapy. Despite considerable interest in this class, drugs like antibiotics also have limitations, and have been neglected. Using new pharmaceutical technologies, the use of magnetic vectors appear as promising candidate for drug delivery systems in several studies. Small magnetic particles bound to the drug of interest can be modulated according to the orientation of a magnet outside the body, locating and holding in a specific site. In this work, we propose the use of High Energy Milling (HEM) for synthesis of a magnetic vector with characteristics suitable for biomedical applications by intravenous administration, and for the formation of an oxacillin-carrier complex to obtain a system for treating infections caused by Staphylococcus aureus. The results of the variation of milling time showed that the size and structural properties of the formed material change with increasing milling time, and in 60 hours we found the sample closest to the ideal conditions of the material. The vector-drug system was studied in terms of structural stability and antimicrobial activity after the milling process, which revealed the integrity of the oxacillin molecule and its bactericidal action on cultures of Staphylococcus aureus ATCC