Thoracic perfusion of Esculentoside A-loaded thermosensitive hydrogel for the treatment of malignant pleural effusion in lung cancer

Malignant pleural effusion (MPE) is a common complication of advanced malignancy with a median survival of less than 5 months. Intrapleural injection is the main treatment for MPE, but there are problems such as the concentration of drugs not being durable and stable in the thoracic cavity, limiting therapeutic efficacy, rapid metabolism of drugs leading to systemic toxicity, a single mechanism of drug. Esculentoside A (EsA) exhibits multi-targeted effects that are potentially valuable to improve the immunosuppressive microenvironment in the thoracic cavity and suppress the development of MPE. But the toxicity and short half-life of EsA severely limit its use. We have developed an EsA delivery system based on a temperature-sensitive hydrogel (PLEL) for local treatment of MPE by intrapleural injection. The EsA/PLEL hydrogel supported slow-release of EsA and maintained a stable intrathoracic drug concentration, which not only significantly inhibited the progression of MPE and prolonged survival, but also reduced the side effects of EsA. We found that downregulating of CXCL1/CXCL2/CXCL3-CXCR2 axis expression to reduce tumour-associated macrophages (TAMs) infiltration and tumour angiogenesis was a potential molecular mechanism for EsA/PLEL hydrogel to control lung cancer MPE. Therefore, this EsA/PLEL hydrogel delivery system has high potential for intrapleural injection therapy of MPE.