Enhanced treatment in cutaneous dermatophytosis management by Zataria multiflora-loaded nanostructured lipid carrier topical gel: A randomized double-blind placebo-controlled clinical trial

Yaser Nasirzadeh Fard, Hamidreza Kelidari, Armaghan Kazemi Nejad, Seyed Jaber Mousavi, Mohammad Taghi Hedayati, Elham Mosayebi, Mojtaba Nabili, Leila Faeli, Kofi Asare-Addo, Ali Nokhodchi, Maryam Moazeni

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The global rising incidence of skin mycosis especially dermatophytes currently affects more than 20–25% of the world population. It is believed that nanotechnology can aid in the efficient treatment of this skin disease. The present study, therefore, aimed to employ nanostructured lipid carriers (NLCs) in a gel formulation for a more effective delivery of Zataria multiflora (ZM) essential oils through the skin to manage mild to moderate cutaneous dermatophytosis. Zataria multiflora-loaded nanostructure lipid carriers (ZM-NLCs) were prepared and optimized by utilizing an ultrasonic probe approach and formulated the ZM-NLCs as a 1% w/w carbopol gel after confirming the NLCs-related characteristics. In vitro antifungal susceptibility testing was performed on 20 common dermatophyte species based on the CLSI M38-A3 guidelines. A total of 80 volunteers (40 volunteers from each gender, equally divided into two groups: ZM-NLCs gel and placebo receivers) participated in this clinical randomized, double-blind placebo-controlled study. Clinical manifestations (itching, scaling, size of lesion and inflammation), as well as mycological findings such as KOH-direct examination test and culture, were evaluated after 2 and 4 weeks of topical application. Molecular identification of the strains isolated from the patient's lesions was also performed to the species level using a PCR-RFLP method. A mono-dispersed suspension of spherical nanoparticles with zeta potential, Z-average and PDI index of −26.6 ± 7.7 mV, 273.5 ± 4 nm and 0.33 ± 0.03, respectively was achieved with no cytotoxicity. Apart from the significant inhibitory effect of ZM-NLCs on fungal growth, the application of the ZM-NLCs gel resulted in an effective diminution in inflammation (87.5%), itching (90%) and scaling (95%) among the volunteers after 4 weeks. The aforementioned signs/symptoms were significant when compared to the patients receiving a placebo (p < 0.005). A reduction/disappearance of the lesion was also significantly reported in the ZM-NLCs gel receivers. Compared with placebo receivers, meaningful negative results for both direct examination and culture were observed (17.5% vs 70% for KOH-direct examination and 12.5% vs 57.5% for culture) for patients who received ZM-NLCs gel after 2 weeks of prescription. PCR-RFLP outputs revealed T. mentagrophytes/interdigitale complex as the predominant isolated species from cutaneous lesions. In conclusion, Zataria multiflora-NLCs gel application displayed a more rapid cure time with no adverse side effects compared to placebo demonstrating the efficacious nature of NLCs.

Original languageEnglish
Article number104132
Number of pages10
JournalJournal of Drug Delivery Science and Technology
Early online date29 Dec 2022
Publication statusPublished - 1 Feb 2023

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