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Nano-Aromatic Drugs For The Treatments Of Neuropsychiatric Disorders

Posted on:2022-09-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z G LuFull Text:PDF
GTID:1481306335964069Subject:Biochemical Engineering
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Neuropsychiatric disorders are generally caused by both external critical stress events and internal genetic factors.The initial stage of neuropsychiatric is a mood disorder.Without intervention,this emotional disorder gradually causes changes in brain physiological activities and eventually develops into neuropsychiatric,placing a heavy burden on individuals,families,and society.Neuropsychiatric disorders require comfortable and gentle interventions to alleviate the patient's mood during the initial mood disorder phase,especially to alleviate the patient's external stress.As an adjuvant therapy,aromatherapy has a significant effect in alleviating stress.However,conventional aromatherapy is not convenient enough.Moreover,the aromatic drug molecules evaporate too quickly,producing too intense aromas and affecting the therapeutic effect.On this basis,we prepared a series of nano-aromatic drugs suitable for daily necessities.According to the wallpaper characteristics used in the daytime but not used at night,we prepared photosensitive nano-aromatic drugs based on inorganic mesoporous silica nanoparticles(MSNs)and organic polymeric micelles,respectively.Besides,according to the silk characteristics used close to the skin and the surface was negatively charged,we prepared pH-responsive nano-aromatic drugs based on cationic micelles and temperature-sensitive responsive nano-aromatic drugs based on cationic liposomes,respectively.We explored nano-aromatic drugs' roles from the behavioral level,tissue level,cell level,and molecular level to better explore nano-aromatic drugs' neuro-regulation.We evaluated the stress relief and anxiolytic effects of the nano-aromatic drugs at the behavioral level through open field tests and elevated plus maze tests.We explored the role of nano-aromatic drugs in neural activity at the tissue level by detecting specific brain regions' physiological potentials.At the cellular level,we explored the role of nano-aromatic drugs in nerve regeneration by immunofluorescence sectioning.At the molecular level,we detected the nano-aromatic drugs' role in neurotransmitter secretion by liquid chromatography-mass spectrometry.Finally,we found that the nano-aromatic drugs had the best neuro-regulation effects,and these effects were long-acting.Stress plays an essential role in the pathogenesis of depression.The nano-aromatic drugs have an excellent stress-relieving effect so that the nano-aromatic drugs have the potential of preventing depression.In the design and preparation of nano-aromatic drugs,inspired by the wallpaper easily moldy,we proposed bionic nano-aromatic drugs.First,according to the fact that most microorganisms are rod-shaped,we prepared the morphology-bionic nano-aromatic drugs based on rod-shaped MSNs.According to the microbial extracellular secretion's effect,especially the polysaccharide extracellular secretion,we modified the chitosan molecules on the surface of the microbial adhesion on the microbial adhesion morphological-bionic nano-aromatic drugs and thus prepared the functional bionic nano-aromatic drugs.Through molecular dynamics simulation,we found that the functional bionic nano-aromatic drugs could generate a large number of hydrogen bonds with the cellulose on the wallpaper and change the spatial structure of cellulose,thus significantly improving the adhesion of the nano-aromatic drugs on the wallpaper.Finally,we endowed the functional bionic nano-aromatic drugs with chemical reaction ability so that the nano-aromatic drugs can form covalent bonds with the wallpaper.We call it bionic plus nano-aromatic drugs.We found that bionic plus nano-aromatic drugs had the best adhesion effect through the adhesion and de-adhesion experiments of nano-aromatic drugs on wallpaper.Subsequently,we induced the depression model mice by injecting corticosterone to create stress.In the stress environment constructed by depression model mice,we adhere the spice-treated wallpaper to the walls of the mouse cage.The results showed that the nano-aromatic drugs had a significant effect on preventing depression compared with the free aromatic drugs.When the mental disorder develops to the extent that the brain's physiological activities are changed,the disease needs to be treated synergistically by aiming at internal genetic factors and external stress factors.In this study,we designed and prepared a gene-aromatic drug delivery system for nasal administration using depression as an example.We introduced Cysteine-odorranalectin to facilitate nasal delivery of the delivery system to the brain.Besides,we introduced sertraline to facilitate targeting of the delivery system to the focal cells.After entering the cells via the endosome,the proton sponge effect excellent in the delivery system expands and breaks the endosome,realizes the endosome's escape,and releases the drug.The gene-drug siRNA can down-regulate serotonin transporter expression,thereby inhibiting serotonin reuptake,improving serotonin content in lesions,and further treating depression by aiming at internal genetic factors.The aromatic drug citral can down-regulate the stress level and treat depression by aiming at external stress factors.The results showed that the gene-aromatic drug delivery system had an excellent synergistic treatment effect for depression.Specific stress environments,such as astronauts' microgravity and loneliness,can cause severe anxiety and cognitive memory decline.The alleviation of stress by nano-aromatic drugs is expected to have a good effect.However,the space environment requires a high degree of cleanliness.That is,the nano-aromatic drugs should be firmly adhered to the daily necessities and not easily de-adhered,In this study,we prepared reactive nano-aromatic drugs by active modification of nano-aromatic drugs.The reactive nano-aromatic drugs can form covalent bonds with the wallpaper,thereby firmly adhering to the wallpaper.We simulated the microgravity and solitary environment of space by hindlimb unloading and replacing the cage walls with ground glass.Furthermore,we explored the role of nano-aromatic drugs in the simulated aerospace special environment.The results showed that the nano-aromatic drugs had significant anti-anxiety and improved cognitive memory.In summary,this study provided a platform for nano-aromatic drugs and controlled release of aromatic drugs.It preliminarily explored the neuro-regulation and mechanism of nano-aromatic drugs,which laid a foundation for the application of nano-aromatic drugs in treating nervous system diseases.Besides,the idea of bionic nano-aromatic drugs was proposed in this study,which significantly improved the adhesion of nano-aromatic drugs on wallpaper and was applied to preventing depression.For the treatment of depression,we proposed a gene-aromatic drug combination therapy strategy and designed and prepared relevant gene-aromatic drug nasal drug delivery systems.Finally,the anti-anxiety and cognitive memory effects of nano-aromatic drugs in the aerospace-specific environment were verified.
Keywords/Search Tags:Nano-Aromatic Drugs with Ability of Slow and Controlled Release, Aroma-Gene Synergistic Treatment, Bionics, Depression, Aerospace-Specific Environment
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