The pulmonary biopharmaceutics and anti-inflammatory effects after intratracheal and intravenous administration of Re-Du-Ning injection - 26/02/23
, Liao Yong-Hong ⁎ Abstract |
Background |
Re-Du-Ning injection (RDN) is a renowned heat-clearing traditional Chinese medicine for the treatment of respiratory diseases owing to its anti-inflammatory effects. However, very little is known about the pulmonary distribution and lung exposure–efficacy relationships. This study aimed to investigate the pulmonary distribution and biopharmaceutics concerning lung penetrability and affinity and the local anti-inflammatory effects after intravenous and pulmonary administration of RDN.
Methods |
Two iridoids and seven phenolic acid components were selected as the chemical markers in RDN. The in vitro pulmonary distribution and biopharmaceutics were conducted by evaluating the binding and disassociation kinetics of chemical markers in lung tissue explants whereas the in vivo evaluation was performed by determining the time-dependent concentrations of chemical markers in plasma, lung epithelial lining fluid (ELF), lung tissues and immune cells in the ELF after intratracheal and intravenous administrations of RDN. The inhibitory effects on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production were used to evaluate the anti-inflammatory effect of RDN on lung tissues in vitro and on mice with LPS-induced lung inflammation.
Results |
The chemical markers of RDN exhibited excellent lung penetrability but poor lung affinity in vitro and in vivo. After intravenous administration, the chemical markers appeared to rapidly penetrate through the lung tissue to reach the ELF, leading to markedly higher drug exposure to ELF and immune cells in the ELF than to lung tissues. Compared to intravenous injection, the intratracheal instillation of RDN increased drug exposure to lung tissue and immune cells in the ELF by up to > 80-fold, leading to improved anti-inflammatory potency and prolonged duration of action.
Conclusion |
The drug exposure to immune cells in the ELF was correlated with the lung-targeted anti-inflammatory effects of RDN and pulmonary delivery has the potential to replace intravenous injection of RDN for the treatment of respiratory diseases.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | The chemical markers of RDN exhibit high lung penetrability but low lung affinity in vitro and in vivo. |
• | Drug exposure to immune cells in the lung epithelial lining fluid is markedly higher than to lung tissues. |
• | Drug exposure to immune cells correlates with the lung targeted anti-inflammatory effects. |
• | Compared to intravenous injection, instilled RDN increases drug exposure to immune cells by up to 84.18-fold. |
• | Compared to intravenous injection, instilled RDN improves anti-inflammatory potency and prolongs the duration of action. |
Abbreviations : BALF, BCS, COPD, DXMS, ELF, ELISA, Fabs, HPLC, IL-6, IT, IV, Kp, Kd, LC-MS, LDH, LOQ, LPS, MAT, MIP-2, MRT, NS, PBS, RDN, RSD, SD，standard deviation；TCM, TNF-α
Keywords : Re-Du-Ning injection, Pulmonary distribution, Pulmonary biopharmaceutics, Inhalation delivery, Anti-inflammation
Plan
Vol 160
Article 114335- avril 2023 Retour au numéro
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