Preparation, optimization, and in vivo evaluation of an inhaled solution of total saponins of Panax notoginseng and its protective effect against idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive pulmonary disease that can cause fibrotic remodeling of the surrounding lung, thus leading to respiratory failure. Although IPF is the most common form of idiopathic interstitial pneumonia, the precise mechanisms underlying this condition remain unknown. In this study, we used total saponins of Panax notoginseng inhalation solution (TIS) to induce idiopathic bleomycin-induced pulmonary fibrosis in rats. The uniformity of delivery dose was investigated by analyzing the aerodynamic particle size distribution and drug stability. The potential of hydrogen potential of hydrogen (pH) of the inhalation solution was 7.0 and the solvent 0.9% NaCl solution, thus meeting physiological requirements for pulmonary drug administration. The delivery rate was 1.94 ± 0.16 mg·min−1 and the total dose was 17.40 ± 0.04 mg. TIS was composed of five key components: notoginsenoside R1, ginsenosides Rg1, ginsenosides Re, ginsenosides Rb1, and ginsenosides Rd. The mass median aerodynamic diameter (MMAD) for these five components were 3.62 ± 0.05 µm, 3.62 ± 0.06 µm, 3.65 ± 0.10 µm, 3.62 ± 0.06 µm, and 3.61 ± 0.05 µm, respectively. Fine particle fraction (FPF) was 66.24 ± 0.73%, 66.20 ± 0.89%, 66.07 ± 1.42%, 66.18 ± 0.79%, and 66.29 ± 0.70%, respectively. The MMAD for inhalation solutions needs to be 1–5 µm, which indicates that the components of TIS are suitable for inhalation. It is important to control the particle size of targeted drugs to ensure that the drug is delivered to the appropriate target tissue. In vitro experiments indicated that TIS exhibited high rates of deposition in lung tissue, thus indicating that pulmonary delivery systems may represent a good therapeutic option for patients.