Sodium butyrate-loaded nanoparticles coated with chitosan for the treatment of neovascularization in age-related macular degeneration: Ocular biocompatibility and antiangiogenic activity.

Sodium butyrate-loaded nanoparticles coated chitosan (NaBu-loaded nanoparticles/CS) were developed to treat the choroidal neovascularization in wet age-related macular degeneration (AMD). The nanoparticles were produced by double emulsification and solvent evaporation technique, optimized by experimental statistical design, characterized by analytical methods, investigated in terms of in vitro and in vivo ocular biocompatibility, and evaluated as an antiangiogenic system in vivo. The NaBu-loaded nanoparticles/CS were 311.1 ± 3.1 nm in diameter with a 0.208 ± 0.007 polydispersity index; had a +56.3 ± 2.6 mV zeta potential; showed a 92.3 % NaBu encapsulation efficiency; and sustained the drug release over 35 days. The NaBu-loaded nanoparticles/CS showed no toxicity to human retinal pigment epithelium cells (ARPE-19 cells); was not irritant to the chorioallantoic membrane (CAM); did not interfere in the integrity of the retinal layers of rat's eyes, as detected by the Optical Coherence Tomography and histopathology; and inhibited the angiogenesis in CAM assay. The NaBu-loaded nanoparticles/CS could be a therapeutic alternative to limit the neovascularization in AMD.

Association of electroanalytical and spectrophotometric methods to evaluate the antioxidant activity of isobenzofuranone in primary cultures of hippocampal neurons.

The isobenzofuran-1(3H)-ones (phthalides) exhibit various biological activities, including antioxidant activity on reactive oxygen species (ROS). An excess of ROS that cannot be naturally contained by cellular enzymatic systems is called redox imbalance, which damage cell membranes, proteins, and DNA, thereby possibly triggering neuronal death in several neurodegenerative diseases. Considering our ongoing efforts to find useful compounds to control redox imbalance, herein we evaluated the antioxidant activity of two phtalides (compounds 3 and 4), using primary cultures of hippocampal neurons. Spectrophotometric assays showed that compound 3 significantly reduced (p ≤ 0.05) ROS levels and lipid peroxidation compared to the control treatment, while compound 4 was unable at any of the tested concentrations. Despite their structural similarity, these compounds behave differently in the intracellular environment, which was reliably corroborated by the determination of oxidation potentials via cyclic voltammetry. It was demonstrated that compound 3 presents a lower oxidation potential. The combination of the mentioned methods allowed us to find a strong correlation between the chemical structure of compounds and their biological effects. Taking together, the results indicate that compound 3 presents desirable characteristics to act as a candidate pharmacological agent for use in the prevention and treatment of neurodegenerative diseases.