1. Academic Validation
  2. Shikonin nasal spray film preparation promoted the repair of nasal mucosal injury by the interaction of shikonin with interleukin-6

Shikonin nasal spray film preparation promoted the repair of nasal mucosal injury by the interaction of shikonin with interleukin-6

  • J Adv Res. 2025 Jun 18:S2090-1232(25)00453-9. doi: 10.1016/j.jare.2025.06.043.
Tao Gao 1 Qingye Jiang 1 Bin Zhang 2 Shenglin Hu 3 Meijing Ye 4 Tianyi Cao 1 Dong Peng 2 Zonghua Zhao 1 Zizhong Tang 1 Yanger Chen 1 Shu Yuan 5 Xiaorong Yan 6 Ming Yuan 7
Affiliations

Affiliations

  • 1 College of Life Science, Sichuan Agricultural University, Yaan 625014, China.
  • 2 Department of Pharmacy & Medical Laboratory, Ya'an Polytechnic College, Yaan 625000 Sichuan, China.
  • 3 Yaan People's Hospital, Yaan 625099, China. Electronic address: 2512363327@qq.com.
  • 4 College of Chemistry and Life Sciences, Chengdu Normal University, Chengdu 611130, China; Sichuan Provincial Key Laboratory for Development and Utilization of Characteristic Horticultural Biological Resources, Chengdu 611130, China.
  • 5 College of Resources, Sichuan Agricultural University, Chengdu 611130, China.
  • 6 Yaan People's Hospital, Yaan 625099, China. Electronic address: 2262810416@qq.com.
  • 7 College of Life Science, Sichuan Agricultural University, Yaan 625014, China; State Key Laboratory Foundation of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: yuanming@sicau.edu.cn.
Abstract

Introduction: Nasal spray films, an innovative formulation in recent years, have garnered significant acclaim from patients with nasal mucosal injury because it integrate the benefits of spray and film formulation, offering ease of application while reducing the risk of droplet formation and further inhalation into the throat. Furthermore, Lithospermum erythrorhizon is a traditional Chinese medicine frequently employed in the management of dermal injuries, and our previous work suggested its major compound, shikonin, possesses the capacity to promote the repair of nasal mucosal injury. Notwithstanding these encouraging results, research on the development of shikonin nasal spray film preparation (SNSF) and its bioactivity mechanism remains limited.

Objectives: This work aimed to formulate SNSF and examine its mechanisms and pharmacokinetic properties in facilitating the repair of nasal mucosal injury, thereby offering insights for its subsequent clinical application.

Methods: The SNSF was prepared, and its structural properties were characterized through particle size analysis, thermogravimetric analysis, scanning electron microscopy, and its material properties, including viscosity, film-forming duration, Moisture absorption, Moisture retention, breathability, and transdermal permeation efficacy, were evaluated. Simultaneously, the repair mechanism of SNSF was explored with RNA-seq, western blotting, RT-PCR, bio-layer interferometry, ultrafiltration affinity, and molecular simulation. Additionally, the pharmacokinetics of SNSF were revealed by HPLC-MS/MS to further demonstrate its clinical application potential.

Results: Shikonin successfully adsorbs on the surface of spray film to obtain SNSF without affecting its material properties. Meanwhile, SNSF treatment significantly alleviated the inflammatory response and facilitated the repair of nasal mucosal injury. This therapeutic effect might be attributed to its active compound, shikonin, which binds to IL-6 and subsequently activates the IL-17 signaling pathway. Additionally, SNSF possessed the characteristics of fast absorption, short half-life, and further enhanced bioavailability of shikonin.

Conclusion: SNSF is a novel candidate drug with great clinical potential for patients with nasal mucosal injury.

Keywords

IL-17 signaling pathway; Nasal mucosal injury; Pharmacokinetics; Shikonin.

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