Preparation of liposomal artesunate dry powder inhalers and the effect on the acute lung injury of rats / 药学学报

ABSTRACT

Artesunate is one of artemisinin derivatives with anti-malarial and anti-inflammatory activities though its water solubility and bioavailability are low. Acute lung injury (ALI) is a seriously dispersive lung disease with a high mortality. In this study, artesunate liposomes were prepared with the film dispersion method, and then lyophilized to obtain the liposomal artesunate dry powder inhalers (LADPIs). The LADPIs were pulmonary-delivered into the lung to treat ALI in rats. The artesunate liposomes had the capsulation efficiency of 71.4%, the particle size of 47.3 nm, and the zeta potential of -13.7 mV. The LADPIs had the aerodynamic particle size of 4.2 μm and the fine particle fraction (FPF) of 34.5%. ALI was established in rats by instilling lipopolysaccharide (LPS) into the lungs. The rats quickly showed a reduction in movement and acceleration in breath followed by diarrhea and so on. The LADPIs were directly administrated into the lungs of ALI rats through airways after 1 h of LPS challenge. The treatment induced a reduction in ALI syndromes. Two inflammatory factors, including TNF-α and IL-6, were significantly reduced by the artesunate powder in the LADPI group similarly to the reduction in the positive drug dexamethasone group (P<0.05). Therefore, the anti-inflammatory effect of LADPIs contributed to the anti-ALI activity. Furthermore, the liposomal formulation improved drug bioavailability in the lung and increased therapeutic efficiency. The LADPIs are promising medicines for therapy of ALI through local drug administration.