Development and in vitro-in vivo performances of an inhalable andrographolide dry powder to target pulmonary inflammation

Andrographolide (AG) is known as a "natural antibiotic". It has been clinically developed into capsules, dropping pills, disperse tablets, etc., for the treatment of viral and bacterial upper respiratory tract infections. It has poor water solubility, obvious P-glycoprotein efflux, and low bioavailability, so its wide application in clinical practice is limited. In this work, a novel AG dry powder inhaler (AG-DPI) was developed using experimental design to optimize the prescription and spray-drying process to obtain higher local concentrations in the lungs while lowering the administered dose; avoiding hepatic first-pass effects and gastrointestinal p-glycoprotein efflux. The short-term local anti-inflammatory effects in the lungs were evaluated using a rat model of acute pneumonia compared with oral administration. The prepared AG-DPI showed that (1) it had good aerosolization properties and was suitable for pulmonary administration, with emitted doses >90%, and fine particle fractions >60%; (2) it was superior to oral administration in the assessment of local anti-inflammatory effects in the lungs by acting on acute pneumonia. This study provides some theoretical value and reference for the inhalable dry powder of AG as a potential targeted treatment modality for lung diseases and infections.