Citation: Xi Kong, Guanlin Wang, Shuhua Wei, Kaiqing Zhang, Yihong Gao, Xiaofan Li, Chuangxin Chen, Ziyu Zhao, Chuanbin Wu, Xuejuan Zhang. Macro-micro spray characteristics of nasal spray: Bridging physicochemical properties to precision olfactory delivery[J]. Chinese Chemical Letters, ;2026, 37(10): 112085. doi: 10.1016/j.cclet.2025.112085 shu

Macro-micro spray characteristics of nasal spray: Bridging physicochemical properties to precision olfactory delivery

Xi Kong ^{a, b, 1} ,
Guanlin Wang ^{c, 1} ,
Shuhua Wei ^a ,
Kaiqing Zhang ^a ,
Yihong Gao ^a ,
Xiaofan Li ^a ,
Chuangxin Chen ^a ,
Ziyu Zhao ^{a, b, *,} ,
Chuanbin Wu ^{a, b, *,} ,
Xuejuan Zhang ^{a, b, *,}

a.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou 511443, China
b.
College of Pharmacy, Jinan University, Guangzhou 511443, China
c.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

zhaoziyu0515@163.com

chuanbinwu@jnu.edu.cn

zhanghongdou0223@126.com

Received Date: 6 April 2025
Revised Date: 6 November 2025
Accepted Date: 6 November 2025
Available Online: 8 November 2025

Figures(4)

The nose-to-brain drug delivery system has emerged as a transformative strategy for central nervous system (CNS) diseases therapy by leveraging the olfactory pathway to circumvent the blood-brain barrier. However, its clinical translation remains impeded by suboptimal olfactory deposition efficiency. A critical but poorly understood challenge lies in rational formulation design, particularly regarding how key physicochemical properties like viscosity govern the nasal drug delivery processes. Using rizatriptan nasal sprays as a viscosity-regulated model system (2–250 mPa s), we dissected how formulation viscosity governs olfactory deposition through synchronized macro-micro spray characteristics. A module 3D-printed human nasal cast was utilized to assess the olfactory deposition efficiency. Additionally, the spray pattern, plume geometry and real-time droplet size distribution were examined using laser diffraction analysis. The results demonstrate a non-monotonic olfactory deposition dependence on viscosity, peaking at 40 mPa s with 31.64% efficiency (31-fold enhancement vs. 2 mPa s). Furthermore, the increase of viscosity led to a reduction in plume angle and spray area, while simultaneously decreasing the stabilization stage fraction of droplets. Mechanistic analysis revealed two competing viscosity-mediated effects: (1) Macroscale plume narrowing that minimized anterior nasal losses; (2) Microscale destabilization of droplets that impaired turbinate transportation. This study elucidates that the viscosity-regulated precision olfactory deposition results from the equilibrium between macroscopic spray geometry and microscopic droplet dynamic, challenging the conventional single-parameter optimization paradigm. Our findings advance nose-to-brain drug delivery by deciphering the viscosity-regulated deposition mechanism, thereby paving the way for rationally designed nasal sprays with enhanced targeting efficiency for CNS diseases.
- Nose-to-brain drug delivery,
- Olfactory deposition,
- Viscosity-regulated strategy,
- Macroscopic spray geometry,
- Microscopic droplet dynamic
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