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

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.