Damp scalp application enhances follicular delivery of dutasteride loaded in liposomes compared to dry scalp.

Dutasteride (DUT) has been increasingly investigated to treat androgenic alopecia topically to minimize systemic side effects. Given evidence that scalp hydration influences drug skin penetration, this study assessed whether applying a DUT-loaded liposome formulation to damp skin enhances DUT deposition compared to dry skin. Skin samples were shampoo-cleansed and either towel-dried or air-dried, followed by treatment with a DUT-loaded liposome formulation. DUT delivery was evaluated in vitro using a modified Saarbrücken model on rodent and porcine skin, with quantification of drug accumulation in viable skin and hair follicles after 12 hours. In rat skin, DUT follicular accumulation nearly doubled on damp skin samples (9.4 ± 1.8 μg/cm2) relative to dry skin (4.7 ± 1.2 μg/cm2, p < 0.05), attributed to enhanced moisture retention in the high follicular density model, which facilitated diffusion. Conversely, porcine skin showed comparable values for damp (10.0 ± 2.1 μg/cm2) and dry (11.8 ± 2.9 μg/cm2) skin conditions, consistent with its lower follicular density and limited capacity to sustain hydration. These findings demonstrate that scalp hydration status can critically modulate topical DUT delivery, particularly in follicle-rich models. Establishing application guidelines considering scalp moisture may improve the clinical performance of topical DUT formulations.