Hydroxy-α-
sanshool (HAS), extracted from Zanthoxylum piperitum, is commonly used in
oral surgery to relief
pain. However, the application of HAS is limited in clinical practice due to its poor stability. This study focuses on the design of a novel nano-formulation delivery system for HAS to improve its stability and
local anesthetic effect. Hydroxy-α-
sanshool loaded nanostructured
lipid carriers (HAS-NLCs) were prepared by melting emulsification and ultra-sonication using monostearate (GMS) and
oleic acid (OA) as
lipid carriers, and poloxamer-188 (F68) as a stabilizer. Besides, the formulation was optimized by response surface methodology (RSM). Then, the best formulation was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%),
drug loading (DL%), differential scanning calorimetry (DSC), and morphology (transmission electron microscopy, TEM). The obtained HAS-NLCs were homogeneous, near spherical particles with high DL% capacity. The stability of HAS-NLCs against
oxygen, light, and heat was greatly improved over 10.79 times, 3.25 times, and 2.09 times, respectively, compared to free HAS. In addition, HAS-NLCs could exhibit sustained release in 24 h following a double-phase kinetics model in vitro release study. Finally, HAS-NLCs had excellent
anesthetic effect at low dose in
formalin test compared with free HAS and
lidocaine, which indicated HAS-NLCs were a potential
local anesthesia formulation in practice.