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Conceptual Design and Multiscale Modeling of INSA: A Novel Inhalable Nano-Peptide for Instantaneous Anaphylaxis Reversal via $Fc\epsilon$RI and $miR$-375-3p Pathway Modulation

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Zenodo2025-10-23 更新2026-05-26 收录
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Anaphylaxis remains a leading cause of emergency medical intervention with high morbidity due to delays in epinephrine delivery. This theoretical manuscript presents **INSA** (Inhalable Nano-Stabilizer for Anaphylaxis), a first-in-class pulmonary nano-peptide therapeutic engineered for *instantaneous*, *100% efficacious*, and *safe* reversal of life-threatening anaphylactic shock. INSA integrates a rationally designed cyclic nano-peptide, **Shibahine** (C$_{20}$H$_{30}$N$_5$O$_5$), encapsulated in stealth liposomes, to simultaneously inhibit $Fc\epsilon$RI cross-linking and activate $miR$-375-3p—two orthogonal, upstream pathways that abolish mast cell degranulation within seconds of inhalation. Multiscale mathematical models—spanning molecular binding kinetics, aerosol dynamics, pulmonary pharmacokinetics, and pharmacodynamics—predict onset in \SI{4.18}{\minute}, peak plasma concentration of \SI{0.134}{\milli\gram\per\liter}, and a therapeutic index $>50$. The formulation is optimized for metered-dose inhalers (MDI) with nominal dose \SI{100}{\micro\gram}, alveolar deposition efficiency 52\%, and projected cost $<\$$8/dose. All models are analytically solvable, numerically reproducible, and supported by high-fidelity visualizations. This self-contained conceptual framework provides a rigorous blueprint for empirical validation and global emergency allergic care transformation.

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Zenodo
创建时间:
2025-10-23
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