Enhanced protective activity of 1,8-cineole on emphysema using hyaluronic acid-coated liposomes via quantitative pulmonary administration in mice

Abstract

Emphysema is a type of chronic obstructive pulmonary disease (COPD) usually leading to difficulty breathing. It is highly in need of effective interventions to prevent airspace damage and stretch. Herein, we studied the protective effect of 1,8-cineole (CIN) on porcine pancreatic elastase (PPE)-induced emphysema in mice via quantitative pulmonary administration. To overcome the volatility, instability and poor water solubility of CIN that limits its pharmacological activities in vivo, a hyaluronic acid (HA)-coated liposome was prepared to encapsulate CIN (Lipo/CIN@HA), which facilitated the delivery of CIN to lung tissue and improved its therapeutic effect for emphysema. A MicrosprayerⓇ aerosolizer was used to deliver free CIN and its liposomal preparations every other day for four weeks and evaluate the therapeutic effects on emphysema in mice. The results clearly showed that CIN significantly reduced the level of inflammation and oxidative stress, resulting in less lung cell apoptosis. Compared with the free CIN and Lipo/CIN, Lipo/CIN@HA exhibited superior protective effects on mice to prevent the PPE-induced emphysema. Furthermore, the therapeutic mechanisms were verified to be mainly mediated by Nrf2/NQO1 and NF-κB/IκBα pathways. In conclusion, quantitative pulmonary administration of CIN could alleviate the progression of emphysema and the therapeutic effects were further improved by the HA-coated liposome carrier.