Hyaluronic acid-based microgels loaded with fluticasone furoate for bleomycin-induced acute lung injury treatment

Bo Liu; Michael Lush; Mollie R Nielsen; Brady J Sillman; Mena Asha Krishnan; Benson J Edagwa; Kristina Bailey; Bin Duan; Han-Jun Wang

doi:10.1016/j.mtbio.2025.102569

Hyaluronic acid-based microgels loaded with fluticasone furoate for bleomycin-induced acute lung injury treatment

Mater Today Bio. 2025 Nov 20:35:102569. doi: 10.1016/j.mtbio.2025.102569. eCollection 2025 Dec.

Authors

Bo Liu^{1

2}, Michael Lush³, Mollie R Nielsen^{1

2}, Brady J Sillman⁴, Mena Asha Krishnan^{1

2}, Benson J Edagwa⁴, Kristina Bailey⁵, Bin Duan^{1

2

6

7}, Han-Jun Wang³

Affiliations

¹ Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
² Division of Cardiovascular Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
³ Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
⁴ Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
⁵ Division of Pulmonary, Critical Care & Sleep Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
⁶ Department of Surgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
⁷ Department of Mechanical and Materials Engineering, University of Nebraska Lincoln, Lincoln, NE, 68588, USA.

Abstract

Acute lung injury (ALI) is a serious clinical condition characterized by intense inflammation and impaired pulmonary function. Excessive inflammatory response and reactive oxygen species (ROS) can cause pulmonary edema and subsequently acute respiratory distress syndrome (ARDS). In this study, we developed fluticasone furoate (FF)-loaded hyaluronic acid (HA)-amino phenylboronic acid (PBA)-epigallocatechin gallate (EGCG) based microgels (HPE@FF) as a novel therapeutic platform for ALI treatment. HPE@FF microgels were prepared by a facile one-pot method, integrating biocompatibility, intrinsic antioxidant and anti-inflammatory properties, and sustained FF delivery. The submicron-size microgels (0.1-1.6 μm) with 93 % encapsulation efficiency effectively reduced intracellular ROS in human lung fibroblast and mouse RAW264.7 cells in vitro. Moreover, HPE@Res significantly downregulated pro-inflammatory gene expressions (Tnf, Il6, and Tgfb) and cytokine secretions (TNF-α and IL-6) in vitro. In a rat model, intratracheal administration of HPE@FF provided prolonged pulmonary retention for up to 28 days, markedly alleviated pulmonary inflammation, improved histological outcomes, and restored lung function and arterial blood gas levels. Collectively, this study presents an innovative microgel-based drug delivery system that advances the design of steroid formulations and offers promising clinical potential for ALI and related respiratory diseases.

Keywords: Acute lung injury; Anti-inflammatory; Antioxidant; Microgel; Pulmonary functions.

Abstract

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