The pulmonary pharmacokinetics and anti-inflammatory effect of anemoside B4 after intratracheal and intravenous administration
10.16438/j.0513-4870.2022-0307
- VernacularTitle:白头翁皂苷B4经气管和静脉给药后的肺部药代动力学与抗炎作用比较研究
- Author:
Chun-yu LIU
1
;
Tao-tao FU
1
;
Fei-fei YANG
1
;
Yu-lin FENG
2
;
Hong-wei GAO
2
;
Shi-lin YANG
2
;
Yong-hong LIAO
1
Author Information
1. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China
2. Guangxi University of Chinese Medicine, Nanning 530200, China
- Publication Type:Research Article
- Keywords:
anemoside B4;
pulmonary inflammation;
pulmonary delivery;
pulmonary bioavailability;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2022;57(9):2791-2797
- CountryChina
- Language:Chinese
-
Abstract:
Anemoside B4 (B4), a main triterpenoid saponin from a traditional Chinese medicine plant, Pulsatilla chinensis, is a novel anti-inflammatory agent for protection from acute lung injury. We investigated the pulmonary availability and anti-inflammatory efficacy of B4 after intratracheal and intravenous dosing with a view to evaluating the suitability of inhalation delivery. All animal studies were performed under the guidelines approved by the Animal Care and Use Committee of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences (Approval No: SLXD-20181113046). In vitro evaluation of the aerodynamic characteristics and droplet size distribution showed that the aerosols generated by a commercially available nebulizer were well deposited in the respiratory tract. Following intratracheal administration, B4 underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 103%. Compared to intravenous delivery, intratracheal administration dramatically increased the drug availability in lung tissue of rats by more than 1 000-fold, leading to improved and prolonged concentrations of B4 in lung tissue up to 48 h. In addition, the intratracheal administration of B4 resulted in dose-dependent and prolonged anti-inflammatory efficacy in a lipopolysaccharide (LPS)-induced lung injury model in mice. The present results demonstrate that inhalation delivery of B4 is a promising approach to treat pulmonary inflammation with once-daily dosing.
