RESUMO
The 5-alpha-reductase enzyme, present in pilosebaceous units, plays a crucial role in the appearance of cutaneous hyperandrogenism manifestations (hirsutism, acne, and androgenetic alopecia). Its inhibition is an excellent strategy to reverse these conditions. Given the limitations of existing treatments, with transient effects and delayed therapeutic response, as well as the possibility of causing undesirable side effects, this study sought to develop new drug delivery systems to overcome these limitations. In other words, innovative stimuli-responsive hybrid nanoparticles were synthesized using silica/natural polysaccharides, encapsulating 5-alpha-reductase enzyme inhibitors derived from the plant Stryphnodendron adstringens (Mart.) Coville (commonly known as 'Barbatimão'). Silica core was synthesized by the modified Stöber method. The pH responsive polysaccharides used to coat the porous silica cores were chitosan, and sodium alginate, this coating was carried out using the Layer-by-Layer technique. The hybrid nanoparticles were characterized at molecular and physical-chemical levels. Furthermore, encapsulation efficiency, pH-dependent release behavior, and cytotoxicity were evaluated. Amorphous mesoporous structure with adequate size for follicular delivery (between 300 and 600 nm) in addition to effective phytocompound loading capacity, above 80 % was obtained. Based on the release studies, it was possible to observe pH responsiveness. The ethyl acetate fraction (EAF) obtained from "Barbatimão" bark extract was released in a controlled and more efficient manner by the alginate-coated nanoparticle (SNP_EAF_SA) at pH 7.4, which corresponds to the pH at the deepest area of hair follicles. Furthermore, SNP_EAF_SA proved to be less cytotoxic compared to EAF and chitosan-coated hybrid nanoparticles (SNP_EAF_CH). Characterization, release, and cytotoxicity results indicate that SNP_EAF_SA is a promising system for on-demand follicular delivery of antiandrogenic actives contained in EAF.
Assuntos
Quitosana , Nanopartículas , Quitosana/química , Inibidores de 5-alfa Redutase , Brasil , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Alginatos/química , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , Oxirredutases , Porosidade , Portadores de FármacosRESUMO
We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.
Assuntos
Doença de Alzheimer , Animais , Feminino , Humanos , Masculino , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Heterozigoto , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Transdução de SinaisRESUMO
The use of smart nanocontainers to store corrosion inhibitors in coatings significantly increases the efficiency and durability of the coating, providing active corrosion protection. Here we report the synthesis of a zinc-layered hydroxide salt (LHS) and its use as a novel nanocontainer for this purpose, storing the corrosion inhibitor molybdate in the interlayer region of the LHS. Layered zinc hydroxide molybdate (ZHM) was obtained by anion-exchange reactions using layered zinc hydroxide acetate (ZHA) as a precursor, obtained by alkaline coprecipitation. The release behavior of molybdate from the ZHM nanocontainers in aqueous NaCl solution (0.05 mol/L) was evaluated using UV-vis absorption spectroscopy. The molybdate release from the ZHM nanocontainers was realized by the anion-exchange mechanism, where chloride anions replaced intercalated molybdate anions. The release was fast in the first minutes of exposure, followed by a controlled release afterward, reaching about 35% of cumulative amount of released molybdate after 30 days of exposure. The anticorrosion effect provided by the ZHM nanocontainers for carbon steel was investigated by electrochemical impedance spectroscopy. The steel substrate was coated with an epoxy resin loaded with ZHM nanocontainers (5 wt %) and immersed in an NaCl solution (0.05 mol/L) to evaluate the active mechanisms of inhibition and the anticorrosion properties of the loaded coating in comparison with a neat coating (blank). The coating loaded with ZHM nanocontainers presented the best corrosion protection performance, exhibiting an increase of RC (coating resistance) with the immersion time and superior RP (polarization resistance) for all the measured periods, compared to the blank. This effect is a consequence of the double mechanism of protection provided by the ZHM nanocontainers: (i) stimulus-response release of molybdate and its active inhibition in the scratched region by the formation of an insoluble protective film, simultaneously with (ii) removal of the corrosive chloride species from the medium.