Drug Design, Development and Therapy (Feb 2019)

Synthesis of budesonide conjugates and their anti-inflammatory effects: a preliminary study

  • Yan Y,
  • Wang P,
  • Li R,
  • Sun Y,
  • Zhang R,
  • Huo C,
  • Xing J,
  • Dong Y

Journal volume & issue
Vol. Volume 13
pp. 681 – 694

Abstract

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Yan Yan,1,2 Pengchong Wang,2 Ruiying Li,3 Ying Sun,2 Rui Zhang,2 Chuanchuan Huo,2 Jianfeng Xing,2 Yalin Dong1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China; 2Department of Pharmaceutics, School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, China; 3Department of Clinical Medicine, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: Budesonide (Bud) is a nonhalogenated glucocorticoid with high anti-inflammatory potency and low systemic side effects. However, the poor water solubility of Bud affects its dissolution and release behavior, thus influencing its anti-inflammatory effect. This study was aimed at synthesizing and evaluating novel conjugates of Bud, hoping to increase the anti-inflammatory activity of Bud by improving its water solubility.Materials and methods: Seven novel Bud conjugates (3a–3g) were designed and synthesized in this study. Besides, the equilibrium solubility, cell viability, in vitro and in vivo anti-inflammatory activity, and the hydrolysis behavior of the conjugates in different pH solutions, rat and human plasma, and rat lung homogenate were studied in detail.Results: As compared to Bud, the equilibrium solubility of 3a, 3c, and 3e was significantly increased; 3a, 3b, and 3c significantly inhibited the interleukin-6 production in lipopolysaccharide-induced A549 cells; 3a and 3e could significantly decrease the xylene-induced ear edema; and 3a and 3c were gradually and slowly hydrolyzed into Bud in the alveolar fluid and lung homogenate and broken down quickly in plasma.Conclusion: The amino acid ester compounds budesonide-21-glycine ester (3a) and budesonide-21-alanine ester (3c) were selected as potential conjugates of Bud. This study would provide a theoretical and an experimental basis for the in vivo process of glucocorticoids and the treatment of inflammatory diseases. Keywords: budesonide, glucocorticoid, anti-inflammatory effect, equilibrium solubility, hydrolysis behavior  

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