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

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 <i>in vitro</i>. Moreover, HPE@Res significantly downregulated pro-inflammatory gene expressions (<i>Tnf</i>, <i>Il6</i>, and <i>Tgfb</i>) and cytokine secretions (TNF-α and IL-6) <i>in vitro</i>. 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.