Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy.
Journal
International journal of biological macromolecules
Journal Volume
280
Journal Issue
Pt 1
Start Page
136149
ISSN
1879-0003
Date Issued
2024-09-29
Author(s)
Abstract
Acute lung injury (ALI), a critical complication of COVID-19, is characterized by widespread inflammation and severe pulmonary damage, necessitating intensive care for those affected. Although glucocorticoids (GCs), such as dexamethasone (Dex), have been employed clinically to lower mortality, their nonspecific systemic distribution has led to significant side effects, limiting their use in ALI treatment. In this study, we explored the conjugation of Dex to hyaluronic acid (HA) to achieve targeted delivery to inflamed lung tissues. We achieved a conjugation efficiency exceeding 98 % using a cosolvent system, with subsequent ester bond cleavage releasing the active Dex, as verified by liquid chromatography. Biodistribution and cellular uptake studies indicated the potential of the HA conjugate for cluster of differentiation 44 (CD44)-mediated targeting and accumulation. In a lipopolysaccharide-induced ALI mouse model, intravenous (IV) HA-Dex administration showed superior anti-inflammatory effects compared to free Dex administration. Flow cytometry analysis suggested that the HA conjugate preferentially accumulated in lung macrophages, suggesting the possibility of reducing clinical Dex dosages through this targeted delivery approach.
Subjects
Acute lung injury
Dexamethasone
Hyaluronic acid
SDGs
Publisher
Elsevier B.V.
Type
journal article