The nasal delivery of nanoencapsulated statins – An approach for brain delivery

© 2016 Clementino et al. Purpose: Along with their cholesterol-lowering effect, statins have shown a wide range of pleiotropic effects potentially beneficial to neurodegenerative diseases. However, such effects are extremely elusive via the conventional oral administration. The purpose of the present study was to prepare and characterize the physicochemical properties and the in vivo biodistribution of simvastatin-loaded lecithin/chitosan nanoparticles (SVT-LCNs) suitable for nasal administration in view of an improved delivery of the statins to the brain. Materials and methods: Chitosan, lecithin, and different oil excipients were used to prepare nanocapsules loaded with simvastatin. Particle size distribution, surface charge, structure, simvastatin loading and release, and interaction with mucus of nanoparticles were determined. The nanoparticle nasal toxicity was evaluated in vitro using RPMI 2651 nasal cell lines. Finally, in vivo biodistribution was assessed by gamma scintigraphy via Tc99m labeling of the particles. Results: Among the different types of nanoparticles produced, the SVT-LCN_MaiLab showed the most ideal physicochemical characteristics, with small diameter (200 nm), positive surface charge (+48 mV) and high encapsulation efficiency (EE; 98%). Size distribution was further confirmed by nanoparticle tracking analysis and electron microscopy. The particles showed a relatively fast release of simvastatin in vitro (35.6%±4.2% in 6 hours) in simulated nasal fluid. Blank nanoparticles did not show cytotoxicity, evidencing that the formulation is safe for nasal administration, while cytotoxicity of simvastatin-loaded nanoparticles (IC50) was found to be three times lower than the drug solution (9.92 vs 3.50 μM). In rats, a significantly higher radioactivity was evidenced in the brain after nasal delivery of simvastatin-loaded nanoparticles in comparison to the administration of a similar dose of simvastatin suspension. Conclusion: The SVT-LCNs developed presented some of the most desirable characteristics for mucosal delivery, that is, small particle size, positive surface charge, long-term stability, high EE, and mucoadhesion. In addition, they displayed two exciting features: First was their biodegradability by enzymes present in the mucus layer, such as lysozyme. This indicates a new Trojan-horse strategy which may enhance drug release in the proximity of the nasal mucosa. Second was their ability to enhance the nose-to-brain transport as evidenced by preliminary gamma scintigraphy studies

Deficiency of Pkc1 activity affects glycerol metabolism in Saccharomyces cerevisiae

In pressProtein kinase C is apparently involved in the control of many cellular systems: the cell wall integrity pathway, the synthesis of ribosomes, the appropriated reallocation of transcription factors under specific stress conditions and also the regulation of N-glycosylation activity. All these observations suggest the existence of additional targets not yet identified. In the context of the control of carbon metabolism, previous data demonstrated that Pkc1 p might play a central role in the control of cellular growth and metabolism in yeast. In particular, it has been suggested that it might be involved in the derepression of genes under glucose-repression by driving an appropriated subcellular localization of transcriptional factors, such as Mig1 p. In this work, we show that pkc1∆ mutant is unable to grow on glycerol because it cannot perform the derepression of GUT1 gene that encodes for glycerol kinase. Additionally, active transport is also partially affected. Using this phenotype, we were able to isolate a new pkc1∆ revertant. We also isolated two transformants identified as the nuclear exportin Msn5 and the histone deacetylase Hos2 extragenic suppressors of this mutation. Based on these results, we postulate that Pkc1 p may be involved in the control of the cellular localization and/or regulation of the activity of nuclear proteins implicated in gene expression.Fundação Universidade Federal de Ouro Preto (FUFOP). Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) - CBS-1875/95. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - 300998/89-9 to R.L.B., 301255/01-6 to L.G.F

EVALUATION OF MYCORRHIZAL INFLUENCE ON THE DEVELOPMENT AND PHYTOREMEDIATION POTENTIAL OF CANAVALIA GLADIATA IN PB-CONTAMINATED SOILS

Soil contamination by heavy metals is a serious problem to humans due to its high level of toxicity. The heavy metal lead (Pb) is commonly used in industries and if the disposal of residues that contain this element is not done properly may result in tragic consequences to the organisms. In this experiment we assessed the potential of a forrage leguminous, Canavalia gladiata, to phytoremediate lead-contaminated soil under mycorrhizal influence. The experimental design was composed of 4 Pb doses (0, 250, 500, and 1000 mg kg(-1) of soil) and the plants were inoculated or uninoculated with arbuscular mycorrhizal fungi (AMF). We observed that the nodulation was severely affected by the presence of Pb independently of the mycorrhizal status; most of the elements analyzed were affected independently of the mycorrhizal status with exception of P. The mycorrhizal colonization was able to restrict the entrance of Pb in plants under high concentrations of Pb but promoted it's accumulation in both organs under intermediate concentrations of this element. Besides the mycorrhization did not promote plant growth under Pb stress, the use of this plant may be considered to be used for phytostabilization purposes.15546547

Copper-64: a real theranostic agent

Bianca Gutfilen,1 Sergio AL Souza,1 Gianluca Valentini2 1Department of Radiology, School of Medicine, Laboratório de Marcação de Células e Moléculas (LMCM), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Advanced Center Oncology Macerata (ACOM), Montecosaro, Italy Abstract: Ongoing studies of physiological and pathological processes have led to a corresponding need for new radiopharmaceuticals, especially when studies are limited by the absence of a particular radiolabeled target. Thus, the development of new radioactive tracers is highly relevant and can represent a significant contribution to efforts to elucidate important phenomena in biology. Currently, theranostics represents a new frontier in the fields of medicine and nuclear medicine, with the same compound being used for both diagnosis and treatment. In the human body, copper (Cu) is the third most abundant metal and it plays a crucial role in many biological functions. Correspondingly, in various acquired and inherited pathological conditions, such as cancer and Alzheimer’s disease, alterations in Cu levels have been found. Moreover, a wide spectrum of neurodegenerative disorders are associated with higher or lower levels of Cu, as well as inappropriately bound or distributed levels of Cu in the brain. In human cells, the membrane protein, hCtr1, binds Cu in its Cu(I) oxidation state in an energy-dependent manner. Copper-64 (64Cu) is a cyclotron-produced radionuclide that has exhibited physical properties that are complementary for diagnosis and/or therapeutic purposes. To date, very few reports have described the clinical development of 64Cu as a radiotracer for cancer imaging. In this review, we highlight recent insights in our understanding and use of 64CuCl2 as a theranostic agent for various types of tumors. To the best of our knowledge, no adverse effects or clinically observable pharmacological effects have been described for 64CuCl2 in the literature. Thus, 64Cu represents a revolutionary radiopharmaceutical for positron emission tomography imaging and opens a new era in the theranostic field. Keywords: Copper-64, theranostic, cancer, radiopharmaceutical, PE