Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy.

Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy.

Publication date: Sep 29, 2024

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.

Concepts Keywords
Cd44 Acute lung injury
Efficiency Dexamethasone
Lipopolysaccharide Hyaluronic acid
Severe
Therapy

Semantics

Type Source Name
drug DRUGBANK Dexamethasone
drug DRUGBANK Hyaluronic acid
disease MESH lung injury
disease MESH COVID-19
disease MESH inflammation
drug DRUGBANK Dextromethorphan

Original Article

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