Application Of Drug Administration Route In Brain Disease Model

Malignant brain tumors,psychiatric diseases,neurodegeneration,mechanical brain injury and other brain diseases have caused a heavy economic burden on patients and the entire society.As the central nervous system of the human body,the brain coordinates human functions and thinking consciousness through neural network connections and the endocrine system.Brain disease severely impairs the patient’s ability to take care of himself in life,causes loss of work ability,and also causes confusion of the patient’s thinking and consciousness,emotional disorders and other symptoms related to mental illness.The pharmacological research of therapeutic drugs for brain diseases is one of the hot researches at home and abroad.Many researchers have devoted a lot of energy to the development of new drugs and new dosage forms for the treatment of brain diseases.However,the blood-brain barrier(BBB)is an important bottleneck in the treatment of brain diseases,preventing all macromolecular drugs and 98% of small molecules from entering the lesion.BBB cells are tightly arranged and are a dense barrier with strict selective permeability.BBB prevents large-molecule drugs lacking corresponding receptors and transporters from entering the brain,and can quickly discharge small-molecule drugs that passively diffuse into the brain,making it difficult for therapeutic drugs to accumulate to an effective concentration.In this paper,three diseases,glioma,drug addiction,and depression,are used as implementation plans to explore whether an appropriate drug delivery method can be selected based on the characteristics of the drug to achieve the effective delivery of new drugs for the treatment of brain diseases,so as to promote the clinical transformation of drugs.The first implementation case of this project is that the injection of paeonol at the solid tumor site can be used to inhibit the deterioration of patients with malignant glioma.First of all,this case confirmed the potential of paeonol in the treatment of malignant glioma through in vitro experiments;secondly,this case confirmed through in vivo experiments that the injection of paeonol into the tumor entity can inhibit the progression of glioma;third;This case further explored the mechanism of paeonol inhibiting the proliferation of malignant gliomas.The results showed that paeonol downregulated the anti-apoptotic factor BCL-2 of malignant glioma cells and upregulated the pro-apoptotic factors BAX BID,BAK.Case I proves that paeonol can be injected directly around the tumor to exert its anti-tumor effect,which proves that small molecule drugs with poor water solubility and high drug concentration can be directly injected into the lesion site with the help of imaging and positioning technology to exert their efficacy.The second practical case of this topic is to verify that intrathecal injection of orphanin can be used to treat behavioral deviation,related physical and chemical indicators and abnormal brain function caused by drug addiction.First,the case constructed a rhesus monkey ketamine addiction model,which successfully simulated the withdrawal symptoms of addicts for the first time;secondly,the case proved that intrathecal injection can exert the analgesic effect of orphanin and relieve the compulsory drug withdrawal.The pain caused by severance specifically includes physical and emotional reduction of the aggression and irritability of the addiction model.Case Ⅱ proved that the intrathecal injection of orphanin was effective in treating drug addiction,which proved that water-soluble peptide drugs with poor self-stability,easy to be catabolized by the liver,kidney or immune cells,and high dosage of water-soluble peptides can be injected intrathecally.The method is transported with the cerebrospinal fluid to the whole ventricle for the treatment of psychiatric diseases with a wide range of nerve projections and complex.The third practical case of this subject is to verify that the new nanoformulation of oxytocin delivered by nasal-brain transport can be used to treat depression.First,in this case,a new type of oxytocin nano-preparation was synthesized by in situ polymerization initiated by free radicals under mild conditions.This nano-material can specifically recognize the cell membrane surface receptors of basal cells and nerve cells in the olfactory zone.After penetrating the nasal mucosa,it can be directly enter the olfactory bulb and spread to the whole brain;secondly,in this case,a lipopolysaccharide-induced depression model(LPS model)was used to evaluate the antidepressant effect of oxytocin nanoformulations.The investigator observed and evaluated the depression-related behaviors of the LPS model after nasal instillation of therapeutic drugs Medicinal effect.Case III proved that the new nano-formulation of oxytocin delivered by nasal-brain transport has the effect of treating depression,which proves that small molecule oligopeptide drugs that are easy to decompose and have a low dosage can be conjugated to materials with functional groups.Biofilm receptors recognize and transport to bypass the BBB to achieve drug delivery into the brain.This study has proved through the above three cases that new drug development can select appropriate drug delivery methods based on drug characteristics to achieve effective delivery of brain disease treatment drugs,so as to accelerate the clinical transformation of drugs.