Dual-drug nanostructured lipid carriers of spironolactone and 2-deoxy-D-ribose for targeted follicular delivery in androgenetic alopecia.

Androgenetic alopecia (AGA) is a multifactorial condition driven by dihydrotestosterone (DHT)-induced follicular miniaturization and reduced perifollicular angiogenesis. Existing treatments such as finasteride, minoxidil, and dutasteride often show limited efficacy and systemic side effects like sexual dysfunction or cardiovascular issues, necessitating targeted approaches. The present study developed dual-drug nanostructured lipid carriers (NLCs) co-delivering spironolactone (SL), an anti-androgen, and 2-deoxy-D-ribose (2dDR), a pro-angiogenic agent, for synergistic follicular regeneration. NLCs were prepared by the hot microemulsion method, incorporating stearic acid as a solid lipid and fenugreek oil as a liquid lipid, with Span 80/Tween 80 surfactants. A Central Composite Design (CCD) was optimised to achieve minimal particle size and optimal zeta potential by varying lipid ratios and surfactant levels. The formulations were characterized by particle size analysis and zeta potential measurements, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and in vitro drug release kinetics. Cytotoxicity and dihydrotestosterone (DHT)-protection assays were performed using human dermal papilla cells (hDPCs). Optimized SL-2dDR NLCs exhibited a particle size of 343.03 ± 9.0 nm, a PDI of 27.97 ± 2.84%, and a zeta potential of -20.13 ± 0.40 mV. Entrapment efficiency reached 99.00 ± 0.5% for SL and 98.75 ± 0.7% for 2dDR. DSC and XRD confirmed amorphous drug dispersion, while SEM revealed irregular, porous morphology favorable for follicular adhesion. In vitro release followed Higuchi kinetics for SL (R2 = 0.994) and Hixson-Crowell for 2dDR (R2 = 0.985). MTT assays demonstrated concentration-dependent cytoprotection against DHT-induced cytotoxicity, maintaining 82% cell viability at 50 µg/mL. The dual-drug NLC system represents a promising targeted therapy for AGA, combining anti-androgenic and pro-angiogenic mechanisms while minimizing systemic exposure.