CD44-targeted hyaluronic acid nanohydrogels enhance macrophage uptake and preserve the anti-inflammatory efficacy of dexamethasone
Abstract
The inflammatory response is among the most critical drivers of tissue damage and systemic dysfunction. Although corticosteroids (CS) can achieve symptom remission and prevent tissue damage, systemic side effects are an issue due to the lack of targeted drug delivery. To this end, we propose a new approach to delivering CS via a hyaluronic acid (HA)-cholesterol nanohydrogel (NHs). Cholesterol, responsible for the formation of NHs, facilitates interactions with CS, while HA interacts with CD44, which is overexpressed on inflammatory cells. The aforementioned NHs were shown to efficiently load dexamethasone (DEX), with 75% drug entrapment efficiency without inducing cytotoxicity in the murine macrophage RAW 264.7 cell line. The ability of DEX to reduce inflammatory cytokine levels in lipopolysaccharide-activated RAW 264.7 cells remained intact when it was loaded into NHs. The empty NHs themselves exhibited anti-inflammatory activity, likely due to the high molecular weight of the HA used in the formulation. Finally, further investigation into the role of HA in immune cell uptake revealed significantly higher internalization by activated macrophages, driven by HA-CD44 interactions, which could enable improved cellular targeting. This nanohydrogel system offers a promising, easily manufactured, and highly biocompatible solution for anti-inflammatory drug delivery.
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BibTeX
@article{migliorini2026cd44targeted,
title = {{CD44-targeted hyaluronic acid nanohydrogels enhance macrophage uptake and preserve the anti-inflammatory efficacy of dexamethasone}},
author = {Claudia Migliorini and Mengyuan Cao and Séverine Domenichini and Mélanie Hery and Giancarlo Tria and Ilaria Silvestri and Pietro Matricardi and Chiara Di Meo and Elias Fattal},
journal = {International Journal of Pharmaceutics},
year = {2026},
month = oct,
doi = {10.1016/j.ijpharm.2026.127535},
url = {https://hal.science/hal-05800321v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CD44-targeted hyaluronic acid nanohydrogels enhance macrophage uptake and preserve the anti-inflammatory efficacy of dexamethasone
AU - Claudia Migliorini
AU - Mengyuan Cao
AU - Séverine Domenichini
AU - Mélanie Hery
AU - Giancarlo Tria
AU - Ilaria Silvestri
AU - Pietro Matricardi
AU - Chiara Di Meo
AU - Elias Fattal
PY - 2026
DA - 2026/10/30
JO - International Journal of Pharmaceutics
DO - 10.1016/j.ijpharm.2026.127535
UR - https://hal.science/hal-05800321v1
AB - The inflammatory response is among the most critical drivers of tissue damage and systemic dysfunction. Although corticosteroids (CS) can achieve symptom remission and prevent tissue damage, systemic side effects are an issue due to the lack of targeted drug delivery. To this end, we propose a new approach to delivering CS via a hyaluronic acid (HA)-cholesterol nanohydrogel (NHs). Cholesterol, responsible for the formation of NHs, facilitates interactions with CS, while HA interacts with CD44, which is overexpressed on inflammatory cells. The aforementioned NHs were shown to efficiently load dexamethasone (DEX), with 75% drug entrapment efficiency without inducing cytotoxicity in the murine macrophage RAW 264.7 cell line. The ability of DEX to reduce inflammatory cytokine levels in lipopolysaccharide-activated RAW 264.7 cells remained intact when it was loaded into NHs. The empty NHs themselves exhibited anti-inflammatory activity, likely due to the high molecular weight of the HA used in the formulation. Finally, further investigation into the role of HA in immune cell uptake revealed significantly higher internalization by activated macrophages, driven by HA-CD44 interactions, which could enable improved cellular targeting. This nanohydrogel system offers a promising, easily manufactured, and highly biocompatible solution for anti-inflammatory drug delivery.
SN - 0378-5173
ER -