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Research On Novel Formulations For Allergic Airway Diseases

Posted on:2024-05-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:J D LiFull Text:PDF
GTID:1521306938457364Subject:Allergic reaction
Abstract/Summary:PDF Full Text Request
Allergic airway diseases(AAD)are chronic diseases characterized by airway inflammation,bronchial constriction,and hyperresponsiveness.In recent years,the number of people affected by AAD has increased dramatically,becoming a significant health burden in China.Inhaled glucocorticoids and bronchodilators are the most commonly used therapeutic drugs,primarily relieving symptoms through antiinflammatory and bronchodilatory effects.However,due to various reasons such as route of administration and compliance,some patients cannot achieve optimal control of symptoms.Allergen-specific immunotherapy(AIT)is the only treatment that can alter the natural course of allergic diseases and achieve long-term efficacy.However,due to the poor-quality control of natural allergen crude extracts used as vaccine,and the complexity and length of AIT treatment,some patients may not experience the expected clinical treatment outcome.Additionally,the premise of performing AIT treatment is good control of clinical symptoms.Based on the above clinical problems,this study conducted research on new formulations for acute symptom control and allergen-specific immunotherapy,respectively.In this study,based on the latest molecular biology and nanoparticle delivery system technology,we successfully prepared two new types of formulations:IL-10-alveolar macrophage cell membrane-coated nanoparticles(IL10-AMNPs)and lipid nanoparticlescoated mRNA vaccines(LNP-mRNA).This study evaluated the two new formulations through cellular and animal models,our results showed that IL10-AMNPs significantly improved the therapeutic effect of IL-10 on allergic airway diseases by reducing airway hyperreactivity,alleviating airway inflammatory cell infiltration,reducing Th1/2/17related cytokine levels,and improving Th17/Treg cell balance.Moreover,we validated for the first time the safety and efficacy of AIT through subcutaneous injection of LNP-mRNA vaccines.This approach improved allergic airway diseases by inhibiting inflammatory cell infiltration,relieving immediate hypersensitivity reactions,inducing Treg cell differentiation,and regulating Thl/Th2 balance.The findings of this study provide new insights and theoretical foundations for the development of novel formulations for the treatment of allergic airway diseases.
Keywords/Search Tags:Allergic airway diseases, Novel formulations, nanoparticle, mRNA, IL-10
PDF Full Text Request
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