Inhaled Dendrimer-Telmisartan Conjugate for Acute Silicosis
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Date
2022-05-12
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Johns Hopkins University
Abstract
Acute silicosis is a disease that happens after inhalation of a large amount of silica, it will further lead to mortality, and the process is irreversible. Current medication is usually the inhalant of inhaled corticosteroids (ICSs) and long-acting beta-agonists (LABAs) as the primary medications. At the same time, it leaves many side effects, including up-regulation of angiotensin II. In this study, we develop an inhalable dendrimer-telmisartan conjugate (D-Tel) to alleviate the progress of acute silicosis via the inhibition of TGF-β activation in an inducible silicosis model based on female wild- type C57BL/6J mice. D-Tel was formulated by chemically attaching telmisartan onto hydroxyl terminated PAMAM G6-OH dendrimer, and performs an efficient pulmonary delivery due to its mucus penetration properties, and it can target the .tivated macrophages. With the biosafety test, the D-Tel and intratracheal administration method has proven reliable. After comparing the treatment of D-Tel (1mg/kg) every 48 hours on a Day 15 and Day 30 biomarker, it is observed that D-Tel can effectively inhibit the activation of TGF-β1. The histological studies revealed that D-Tel successfully alleviates fibrosis progression and has anti-inflammation properties. Therefore, D-Telmisartan conjugation creates a practical option to develop silicosis management clinically with less dosing frequency and more minor side effects.
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Keywords
Dendrimer, conjugates, acute silicosis