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 constructed fluticasone furoate (FF)-loaded hyaluronic acid (HA)-epigallocatechin gallate (EGCG)-amino phenylboronic acid (PBA) based microgels (referred to as HPE microgels), which exhibited good biocompatibility as well as anti-ROS and anti-inflammatory properties for the treatment of ALI. The HPE@FF microgels were fabricated by a facile one-pot approach that integrated bio-functional EGCG molecules and therapeutic FF molecules. The HPE@FF with submicron-size (0.1~1.6 µm) and 93% encapsulation efficiency of FF significantly reduced intracellular ROS in human lung fibroblast and mouse RAW264.7 cells in vitro. In addition, HPE@FF could downregulate several pro-inflammatory gene expressions (such as Tnf, Il6, and Tgfb) and cytokine secretions (such as TNF-α and IL-6) in RAW264.7 cells in vitro. Furthermore, we performed the intratracheal injection of HPE@FF microgels in rat experiencing ALI and found that the retention time of such microgel was up to 28 days in lung tissue, demonstrating its promising therapeutic drug delivery efficiency in ALI therapy. The histological staining revealed that HPE@FF microgels intervention significantly decreased acute lung inflammation, compared to the ALI model group. We also showed that HPE@FF treatment improved both respiratory functions and arterial blood gas level in ALI rats. Altogether, this study presents a versatile drug delivery system for the locally intratracheal delivery of FF therapeutics to alleviate ALI, demonstrating promising clinical potential for the treatment of respiratory diseases.