Browsing by Author "Milic Torres, Vukosava"
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- Biomedical Application of FullerenesPublication . Milic Torres, Vukosava; Srdjenovic, Branislava; Verner, Robert F.; Benvegnu, CarlosFullerene, the third carbon allotrope, is a classical engineered material with the potential application in biomedicine. Since their discovery in 1985, fullerenes have been extensively investigated. The biological activities of fullerenes are considerably influenced by their chemical modifications and light treatment. The most relevant feature of fullerene C60 is the ability to act as a free radical scavenges. Properties attributed to the delocalized π double bond system of fullerene cage allow C60 to quench various free radicals more efficiently than conventional antioxidants. However, extremely high hydrophobicity of fullerene hampers its direct biomedical evaluation and application. To overcome this problem, several approaches for the transfer fullerenes into physiological friendly media have been developed: chemical modification of the fullerene carbon cage, incorporation of fullerenes into water soluble micellar supramolecular structures, solvent exchange and long term stirring of pure C60 in water. These steps created army of different classes of functionalized fullerenes which exhibit vast range of biological activities, especially in the field of photodynamic therapy, neuroprotection, apoptosis, drug and gene delivery. It was found that certain classes of functionalized fullerenes can be used for diagnostic purposes. So far, the most promising applications include the use of gadolinium endohedral complexes in magnetic resonance imaging and therpautic (as a primary or adjuvant) exploration of tris-adducts and polyhidroxlated C60 fullerenes. In this chapter we are summarizing and discussing main biological and medicinal aspects of fullerenes and its functionalized derivates with special regards to the recent achievements.
- Doxorubicin-induced oxidative injury of cardiomyocytes - do we have right strategies for prevention?Publication . Milic Torres, Vukosava; Dragojevic Simic, ViktorijaAnthracyclines are among the most utilised antitumour drugs ever developed. The discovery of one of the leading compounds, doxorubicin (DOX) in early 1960s was a major advance in the fight against cancer. According to the WHO, it belongs to the group of 17 essential drugs that are used to treat curable cancers or cancers for which the cost-benefit ratio clearly favours drug treatment (Sikora et al., 1999). It is used, often with other antineoplastic, in the treatment of Hodgkin's disease, non-Hodgkin's lymphomas, acute leukaemias, bone and soft-tissue sarcoma, neuroblastoma, Wilm's tumour, and malignant neoplasms of the bladder, breast, lung, ovary, and stomach. The mechanisms of cytotoxicity of DOX in cancer cells is complex including: inhibition of both DNA replication and RNA transcription; free radicals generation, leading to DNA damage or lipid peroxidation; DNA cross-linking; DNA alkylation; direct membrane damage due to lipid oxidation and inhibition of topoisomerase II (Gewirtz, 1999; Minotti et al., 2004). Today, topoisomarase II is generally recognized to be the cellular target of DOX, which act by stabilizing a reaction intermediate in which DNA strands are cut and covalently linked to this enzyme (Simunek et al., 2009). It blocks subsequent DNA resealing. Failure to relax the supercoiled DNA blocks DNA replication and transcription. Furthermore, DNA strand breaks may trigger apoptosis of cancer cells. However, as with all traditional antineoplastic drugs, DOX administration is accompanied by adverse drug reactions arising from the limited selectivity of their anticancer action (Aronson et al., 2006; McEvoy et al., 2010). Particularly common are bone marrow depression, which may be dose-limiting. White cell count reaches a nadir 10 to 15 days after a dose and usually recovers by about 21 days. Gastrointestinal disturbances include moderate or sometimes severe nausea and vomiting; stomatitis and oesophagitis may progress to ulceration. Alopecia occurs in the majority of patients. Occasional hypersensitivity reactions may also occur. However, a cumulative-dose dependent cardiac toxicity has been a major limitation of DOX use.
- Solubilization of fullerene C60 in micellar solutions of different solubilizersPublication . Milic Torres, Vukosava; Posa, Mihalj; Srdjenovic, Branislava; Simplício, Ana LuísaFullerene (C(60)), the third carbon allotrope, is a classical engineered material with the potential application in biomedicine. However, extremely high hydrophobicity of fullerene hampers its direct biomedical evaluation and application. In this work, we investigated the solubilization of fullerene using 9 different solubility enhancers: Tween 20, Tween 60, Tween 80, Triton X-100, PVP, polyoxyethylene (10) lauryl ether, n-dodecyl trimethylammonium chloride, myristyl trimethylammonium bromide and sodium dodecyl sulphate and evaluated its antioxidant activity in biorelevant media. The presence of C(60) entrapped in surfactant micelles was confirmed by UV/VIS spectrometry. The efficacy of each modifier was evaluated by chemometric analysis using experimental data for investigating the relationship between solubilization and particle size distribution. Hierarchical clustering and principal component analysis was applied and showed that non-ionic surfactants provide better solubilization efficacy (>85%). A correlation was established (r=0.975) between the degree of solubilization and the surfactant structure. This correlation may be used for prediction of C(60) solubilization with non-tested solubility modifiers. Since the main potential biomedical applications of fullerene are based on its free radical quenching ability, we tested the antioxidant potential of fullerene micellar solutions. Lipid peroxidation tests showed that the micellar solutions of fullerene with Triton and polyoxyethylene lauryl ether kept high radical scavenging activity, comparable to that of aqueous suspension of fullerene and BHT. The results of this work provide a platform for further solubilization and testing of pristine fullerene and its hydrophobic derivatives in a biological benign environment.