Department of Chinese Medicinal Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Yang Guang South Street, Fangshan District, Beijing, 102488, China.
Drug Deliv Transl Res. 2021 Oct;11(5):1958-1968. doi: 10.1007/s13346-020-00857-7. Epub 2020 Oct 3.
Salvianolic acids (SAL), the main bioactive component extracted from Salvia miltiorrhiza, is a natural product with a reported anti-pulmonary fibrosis (PF) effect. SAL is commonly administrated orally; however, it has a low oral bioavailability (less than 5%). The objective of this work was to develop a new dry powder inhalable formulation intended to facilitate the access of SAL to the target place. We prepared the new SAL powder formulation containing L-arginine and 2% of lecithin using the ball milling technique. L-arginine was used to regulate the strong acidity of the SAL solution, and lecithin was added to disperse the powder and improve the flowability. The resulting powder had a content in salvianolic acid B (SALB, the main active principle of SAL) of 66.67%, a particle size of less than 5 μm and a good flowability. In vivo fluorescence imaging showed that the powder could be successfully aerosolized and delivered to the lung. The acute lung irritation study proved that the presence of L-arginine improved the biocompatibility of the powder. Finally, according to the pharmacokinetic study, the new SAL powder formulation was found to significantly increase drug concentration in the lung and the bioavailability. In conclusion, the new dry powder inhalable formulation of SAL developed in this study could be a strategy to enhance the performance of SAL at the lung level. Graphical abstract.
丹酚酸 B（SALB，SAL 的主要活性成分）含量为 66.67%，粒径小于 5μm，流动性好。体内荧光成像显示，该粉末可成功雾化并输送到肺部。急性肺刺激研究证明，精氨酸的存在提高了粉末的生物相容性。最后，根据药代动力学研究，新的 SAL 干粉吸入制剂显著增加了肺部的药物浓度和生物利用度。总之，本研究开发的新丹酚酸 SAL 干粉吸入制剂可能是提高 SAL 肺部疗效的一种策略。
