RESUMO
Drug delivery to the brain is challenging because of the low permeability of blood-brain barrier, and therefore, optimum concentration of chemotherapeutics in the target area specifically for glioblastoma, an aggressive brain tumor, opens a new path of research. To achieve the goal, the oral alkylating agent temozolomide was incorporated into niosomes, and the surface was modified with chlorotoxin, a small 36 amino acid peptide discovered from the venom of scorpion Leiurus quinquestriatus. Active targeting using nanosized particles facilitates an increase in the accumulation of drugs in the cerebri by 3.04-folds. Temozolomide-loaded niosomes were prepared using conventional thin-film hydration method and characterized. Niosomes coated with chlorotoxin were produced with the size of 220 ± 1.45 nm with an entrapment efficiency of 79.09 ± 1.56%. Quantitative tissue distribution studies indicate enhanced permeation of the drug into the brain because of surface modification with less deposition in the highly perfused organs.
RESUMO
The concentrations of anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and selenium-dependent glutathione peroxidase (SeGPx), and low molecular weight free-radical scavengers such as reduced glutathione (GSH) and ascorbic acid (vitamin C) were evaluated during the period from gastrulation (GS) to 25 days post-hatch (dph) in the larvae of Asian Seabass, Lates calcarifer. Oxidative damage due to lipid peroxidation (LPO) was also assessed, by evaluation of the formation of malondialdehyde (MDA). All the three anti-oxidant enzymes, SOD, CAT and GPx, showed high activities during gastrulation, suggesting an increased metabolic rate during the period of embryonic development. Though the SOD activity apparently decreased progressively during 3-20 dph of larval development, the difference was not significant. CAT showed high activity during gastrulation and remained constant up to 3 dph, suggesting an increased need to metabolise hydrogen peroxide (H2O2) and organic peroxides. In contrast, SeGPx activity increased progressively from 5 dph to 25 dph during larval development, indicating an increased need to detoxify lipid peroxides. This is evident from the observation of increased lipid peroxidation from 10 dph to 25 dph during larval development. GSH levels were low at gastrulation, indicating increased metabolic rate and formation of lipid radicals during this period, corresponding to the decrease in the level of ascorbic acid, which is consumed for regeneration of GSH.
