Leeyaphan C.Punnakitikashem P.Suiwongsa B.Komesmuneeborirak P.Chongtrakool P.Kulthanachairojana N.Limphoka P.Hutachoke T.Saengthong-aram P.Kobkurkul P.Wongdama S.Pongkittilar B.Matthapan L.Panyawong C.Prasong W.Plengpanich A.Kunwong N.Rodponthukwaji K.Bunyaratavej S.Mahidol University2025-02-162025-02-162025-01-01Dermatology and Therapy (2025)21938210https://repository.li.mahidol.ac.th/handle/20.500.14594/105312Introduction: A novel antifungal formulation combining zinc oxide nanoparticles and Whitfield’s spirit solution (ZnO-WFs) was developed to enhance the treatment of superficial fungal foot infections. Methods: This 8-week, randomized, double-blinded controlled trial compared the efficacy, safety, and cost-effectiveness of ZnO-WFs with those of Whitfield’s spirit solution (WFs) alone and a zinc oxide nanoparticle solution (ZnOs). Seventy of the 84 enrolled patients completed the trial. Results: Patients treated with ZnO-WFs and WFs showed similar mycological cure rates, significantly outperforming ZnOs at the 4-week and 8-week evaluations (65.2% and 81.8% for ZnO-WFs and 66.7% and 83.3% for WFs, respectively, compared to 4.0% and 16.7% for ZnOs; P < 0.001). Particularly in nondermatophyte mold (NDM) infections, ZnO-WFs tended to have greater cure rates than WFs (90.0% vs 44.4% at 4 weeks, P = 0.057; 90.0% vs 55.6% at 8 weeks, P = 0.141). Patient satisfaction was equivalent across all groups. The cost-effectiveness analysis revealed that ZnO-WFs is a more economical option for managing NDM infections. Conclusion: This study confirmed that both ZnO-WFs and WFs effectively treat superficial fungal foot infections. However, ZnO-WFs demonstrates a trend toward increased efficacy and lower cost per patient in managing NDM infections, suggesting a potential advantage over WFs in these specific cases. Trial Registration: ClinicalTrials.gov identifier, NCT05901961.MedicineArticleSCOPUS10.1007/s13555-025-01340-22-s2.0-8521716693521909172