Objective To enhance the hair follicle-targeted delivery efficiency of cedrol, a cedrol nanosuspension (Ce-NS) was prepared. The formulation and process parameters were optimized, the physicochemical properties were characterized, and its therapeutic efficacy in the treatment of androgenetic alopecia (AGA) was evaluated. Methods Ce-NS was prepared using a solvent-antisolvent precipitation method. Based on single-factor experiments, particle size and polydispersity index (PDI) were selected as evaluation parameters to optimize the formulation and process variables using the Box-Behnken design-response surface methodology (BBD-RSM). The physicochemical characteristics and storage stability of the formulation were determined by dynamic light scattering (DLS). In vitro transdermal performance was evaluated using a Franz diffusion cell system. Morphological characteristics were examined by scanning electron microscopy (SEM) to assess the accumulation of nanocrystals within hair follicles. An AGA model was established in C57BL/6 mice. Hematoxylin-eosin (HE) staining and immunohistochemical analysis of dorsal skin tissues were performed to evaluate the in vivo hair growth-promoting efficacy. Results The optimal formulation parameters were as follows: cedrol mass concentration 7.5 mg/mL, sodium dodecyl sulfate (SDS) 170 mg, hydroxypropyl methylcellulose (HPMC) 130 mg, and a polyethylene glycol (PEG) 400-to-water phase ratio of 1∶12. The process parameters included a dropping rate of 20 mL/min, stirring speed of 10 000 r/min, and shearing time of 5 min. The prepared Ce-NS exhibited a mean particle size of (434.47 ± 9.90) nm, a PDI of 0.232 ± 0.005, and a ζ potential of (&8722;15.20 ± 1.15) mV. The experimental values were in good agreement with the predicted values of the model. Ce-NS remained stable for 90 days at room temperature. In vitro transdermal studies showed that the skin retention of Ce-NS within 24 h reached (74.38 ± 3.90) μg/cm2, which was 4.1-fold higher than that of the raw drug group, while no cedrol was detected in the receptor medium. SEM observation of skin sections confirmed the accumulation of cedrol nanocrystals within hair follicles. Pharmacodynamic evaluation demonstrated that, compared with the model group, Ce-NS significantly promoted hair regeneration in AGA model mice, increased hair follicle density and hair length, decreased androgen receptor (AR) expression in dorsal skin tissue, and upregulated the expression of Ki67 and β-catenin. Conclusion Ce-NS was successfully prepared using a green preparation process and exhibited stable physicochemical properties. The formulation significantly enhanced the skin retention and follicular targeting of cedrol, demonstrating promising therapeutic potential for androgenetic alopecia. The underlying mechanism may be associated with the downregulation of androgen signaling and activation of the Wnt/β-catenin pathway.

cedrol  /  polyethylene glycol 400  /  nanosuspensions  /  androgenetic alopecia  /  hair regeneration