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Article Dans Une Revue International Journal of Pharmaceutics Année : 2023

Hyaluronic acid-conjugated liposomes loaded with dexamethasone: A promising approach for the treatment of inflammatory diseases

Résumé

Dexamethasone is a well-known anti-inflammatory drug readily used to treat many lung diseases. However, its side effects and poor lower airway deposition and retention are significant limitations to its usage. In this work, we developed lipid nanoparticulate platforms loaded with dexamethasone and evaluated their behavior in inflammatory lung models in vitro and in vivo. Dexamethasone-loaded liposomes with an average diameter below 150 nm were obtained using a solvent injection method. Three different formulations were produced with a distinct surface coating (polyethylene glycol, hyaluronic acid, or a mixture of both) as innovative strategies to cross the pulmonary mucus layer and/or target CD44 expressed on alveolar proinflammatory macrophages. Interestingly, while electron paramagnetic spectroscopy showed that surface modifications did not induce any molecular changes in the liposomal membrane, drug loading analysis revealed that adding the hyaluronic acid in the bilayer led to a decrease of dexamethasone loading (from 3.0 to 1.7w/w%). In vitro experiments on LPS-activated macrophages demonstrated that the encapsulation of dexamethasone in liposomes, particularly in HA-bearing ones, improved its anti-inflammatory efficacy compared to the free drug. Subsequently, in vivo data revealed that while intratracheal administration of free dexamethasone led to an important interanimals variation of efficacy, dexamethasone-loaded liposomes showed an improved consistency within the results. Our data indicate that encapsulating dexamethasone into lipid nanoparticles is a potent strategy to improve its efficacy after lung delivery.
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Dates et versions

hal-04173093 , version 1 (28-07-2023)

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Kamila Bohne Japiassu, Francois Fay, Alessandro Marengo, Sebastião A Mendanha, Catherine Cailleau, et al.. Hyaluronic acid-conjugated liposomes loaded with dexamethasone: A promising approach for the treatment of inflammatory diseases. International Journal of Pharmaceutics, 2023, 639, pp.122946. ⟨10.1016/j.ijpharm.2023.122946⟩. ⟨hal-04173093⟩
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