Pulmonary Delivery of Levamisole Nanoparticles as an Immunomodulator Affecting Th and a Potential ADAM10 Inhibitor to Ameliorate Severe Allergic Asthma
| Autor: | Liping Fang, Nasser Nikfarjam, Mohammad Gharagozlou, Tao Huang, Yu Song, Ziba Islambulchilar, Abdolreza Esmaeilzadeh, Davood Jafari, Seyyed Shamsadin Athari |
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| Rok vydání: | 2022 |
| Předmět: |
Ovalbumin
Biomedical Engineering Biomaterials ADAM10 Protein Mice Animals Immunologic Factors Lung Interleukin-13 Tumor Necrosis Factor-alpha Interleukin-17 Membrane Proteins Forkhead Transcription Factors Immunoglobulin E Nuclear Receptor Subfamily 1 Group F Member 3 Interleukin-33 Asthma Interleukin-10 Levamisole Immunoglobulin G Cytokines Interleukin-2 Nanoparticles Interleukin-4 Amyloid Precursor Protein Secretases Interleukin-5 Bronchoalveolar Lavage Fluid |
| Zdroj: | ACS Biomaterials Science & Engineering. 8:4566-4576 |
| ISSN: | 2373-9878 |
| DOI: | 10.1021/acsbiomaterials.2c00843 |
| Popis: | Asthma is a common chronic lung disease without absolute treatment, and hypersensitivity reactions and type 2 immune responses are responsible for asthma pathophysiology. ADAM10 as a metalloproteinase transmembrane protein is critical for development of Th2 responses, and levamisole as an anthelmintic drug has immunomodulatory effects, which not only regulates ADAM10 activity but also can suppress the bone marrow and neutrophil production. Therefore, in the present study, nanoparticles were used as a levamisole delivery system to reduce bone marrow suppression, and the immunomodulatory and ADAM10 inhibitory effects of levamisole were studied in allergic asthma. Asthmatic mice were treated with PLGA-levamisole nanoparticles. Then, AHR, BALF, and blood cell counts, levels of the IgG1 subclass, total and OVA-specific IgE, IL2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-25, IL-33, INF-γ, and TNF-α, gene expression of FoxP3, T-bet, RORγt, PU.1, GATA3, FcεRII, CysLT1R, eotaxin, and ADAM10, and lung histopathology were evaluated. PLGA-LMHCl with considered characteristics could control airway hyper-responsiveness, eosinophils in the BALF, levels of immunoglobulins, Th2-, Th9-, and Th17-derived cytokines and pivotal genes, eosinophilic inflammation, hyperplasia of the goblet cell, and hyperproduction of mucus and could increase Th1- and Treg-derived cytokines and also pivotal genes. It could also modulate the ADAM10 activity and had no effect on the number of neutrophils in the bloodstream. The novel safe nanodrug had no side effect on the bone marrow to produce neutrophils and could control the allegro-immuno-inflammatory response of asthma. |
| Databáze: | OpenAIRE |
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