{"title":"特比萘芬-纳米结构脂质载体的双盲随机临床试验：我们是否应该期待这种有效的局部治疗甲真菌病的策略？","authors":"Shima Parsay, Majid Saeedi, Mahdi Abastabar, Mohammad Taghi Hedayati, Seyyed Mobin Rahimnia, Nasim Gholizadeh, Armaghan Kazeminejad, Katayoun Morteza-Semnani, Roozbeh Zare Gashti, Kofi Asare-Addo, Maryam Moazeni, Ali Nokhodchi","doi":"10.1111/myc.70076","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Oral terbinafine (TBF) is the drug of choice for onychomycosis management. To treat and heal the rough and thick nail tissue affected by fungal agents, a high dose and plasma concentration of this drug is necessary. This, however, poses a life-threatening risk due to the cytotoxic side effects, drug-drug interactions, and adverse physical and chemical properties associated with oral medications.</p><p><strong>Objectives: </strong>This study aimed to employ nanostructured lipid carriers (NLCs) in a gel formulation to avoid side effects and to increase the absorption of topical TBF.</p><p><strong>Methods: </strong>Terbinafine-loaded nanostructured lipid carriers (TBF-NLCs) were developed and optimised using an ultrasonic probe technique, resulting in the formulation of TBF-NLCs as a 1% w/w carbopol gel after verifying the characteristics associated with NLCs. In vitro antifungal susceptibility test (AFST) was conducted on 85 prevalent fungal species associated with onychomycosis, as well as on strains isolated from trial participants, following the CLSI M38-A2 and M27-A3 guidelines. A total of 60 volunteers were enrolled in this clinical randomised, double-blind, placebo-controlled study, divided equally into three groups prescribed with TBF cream 1%, TBF-NLCs gel 1%, and a placebo.</p><p><strong>Results: </strong>A monodisperse suspension of spherical nanoparticles was successfully produced, exhibiting a zeta potential of 18.4 ± 1.02 mV, a Z-average of 131.7 ± 5.32 nm, a PDI index of 0.280 ± 0.017, and an EE percentage of 83.51 ± 3.52, all without any cytotoxic effects. The severity index showed a reduction from 65% and 55% to 35% and 10% in the TBF cream 1% and TBF-NLCs groups, respectively. From a mycological perspective, no significant negative results were noted during the 6th and 8th weeks of TBF-NLC 1% gel application.</p><p><strong>Conclusion: </strong>The application of TBF-NLCs gel 1% demonstrated a quicker clinical recovery without adverse side effects compared to TBF cream, thus highlighting the effective nature of NLCs.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"68 6","pages":"e70076"},"PeriodicalIF":3.1000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171949/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Double-Blind Randomised Clinical Trial of Terbinafine-Nanostructured Lipid Carriers: Should We Anticipate This Strategy for Effective Topical Treatment of Onychomycosis?\",\"authors\":\"Shima Parsay, Majid Saeedi, Mahdi Abastabar, Mohammad Taghi Hedayati, Seyyed Mobin Rahimnia, Nasim Gholizadeh, Armaghan Kazeminejad, Katayoun Morteza-Semnani, Roozbeh Zare Gashti, Kofi Asare-Addo, Maryam Moazeni, Ali Nokhodchi\",\"doi\":\"10.1111/myc.70076\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Oral terbinafine (TBF) is the drug of choice for onychomycosis management. To treat and heal the rough and thick nail tissue affected by fungal agents, a high dose and plasma concentration of this drug is necessary. This, however, poses a life-threatening risk due to the cytotoxic side effects, drug-drug interactions, and adverse physical and chemical properties associated with oral medications.</p><p><strong>Objectives: </strong>This study aimed to employ nanostructured lipid carriers (NLCs) in a gel formulation to avoid side effects and to increase the absorption of topical TBF.</p><p><strong>Methods: </strong>Terbinafine-loaded nanostructured lipid carriers (TBF-NLCs) were developed and optimised using an ultrasonic probe technique, resulting in the formulation of TBF-NLCs as a 1% w/w carbopol gel after verifying the characteristics associated with NLCs. In vitro antifungal susceptibility test (AFST) was conducted on 85 prevalent fungal species associated with onychomycosis, as well as on strains isolated from trial participants, following the CLSI M38-A2 and M27-A3 guidelines. A total of 60 volunteers were enrolled in this clinical randomised, double-blind, placebo-controlled study, divided equally into three groups prescribed with TBF cream 1%, TBF-NLCs gel 1%, and a placebo.</p><p><strong>Results: </strong>A monodisperse suspension of spherical nanoparticles was successfully produced, exhibiting a zeta potential of 18.4 ± 1.02 mV, a Z-average of 131.7 ± 5.32 nm, a PDI index of 0.280 ± 0.017, and an EE percentage of 83.51 ± 3.52, all without any cytotoxic effects. The severity index showed a reduction from 65% and 55% to 35% and 10% in the TBF cream 1% and TBF-NLCs groups, respectively. From a mycological perspective, no significant negative results were noted during the 6th and 8th weeks of TBF-NLC 1% gel application.</p><p><strong>Conclusion: </strong>The application of TBF-NLCs gel 1% demonstrated a quicker clinical recovery without adverse side effects compared to TBF cream, thus highlighting the effective nature of NLCs.</p>\",\"PeriodicalId\":18797,\"journal\":{\"name\":\"Mycoses\",\"volume\":\"68 6\",\"pages\":\"e70076\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171949/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mycoses\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/myc.70076\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mycoses","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/myc.70076","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
A Double-Blind Randomised Clinical Trial of Terbinafine-Nanostructured Lipid Carriers: Should We Anticipate This Strategy for Effective Topical Treatment of Onychomycosis?
Background: Oral terbinafine (TBF) is the drug of choice for onychomycosis management. To treat and heal the rough and thick nail tissue affected by fungal agents, a high dose and plasma concentration of this drug is necessary. This, however, poses a life-threatening risk due to the cytotoxic side effects, drug-drug interactions, and adverse physical and chemical properties associated with oral medications.
Objectives: This study aimed to employ nanostructured lipid carriers (NLCs) in a gel formulation to avoid side effects and to increase the absorption of topical TBF.
Methods: Terbinafine-loaded nanostructured lipid carriers (TBF-NLCs) were developed and optimised using an ultrasonic probe technique, resulting in the formulation of TBF-NLCs as a 1% w/w carbopol gel after verifying the characteristics associated with NLCs. In vitro antifungal susceptibility test (AFST) was conducted on 85 prevalent fungal species associated with onychomycosis, as well as on strains isolated from trial participants, following the CLSI M38-A2 and M27-A3 guidelines. A total of 60 volunteers were enrolled in this clinical randomised, double-blind, placebo-controlled study, divided equally into three groups prescribed with TBF cream 1%, TBF-NLCs gel 1%, and a placebo.
Results: A monodisperse suspension of spherical nanoparticles was successfully produced, exhibiting a zeta potential of 18.4 ± 1.02 mV, a Z-average of 131.7 ± 5.32 nm, a PDI index of 0.280 ± 0.017, and an EE percentage of 83.51 ± 3.52, all without any cytotoxic effects. The severity index showed a reduction from 65% and 55% to 35% and 10% in the TBF cream 1% and TBF-NLCs groups, respectively. From a mycological perspective, no significant negative results were noted during the 6th and 8th weeks of TBF-NLC 1% gel application.
Conclusion: The application of TBF-NLCs gel 1% demonstrated a quicker clinical recovery without adverse side effects compared to TBF cream, thus highlighting the effective nature of NLCs.
期刊介绍：
The journal Mycoses provides an international forum for original papers in English on the pathogenesis, diagnosis, therapy, prophylaxis, and epidemiology of fungal infectious diseases in humans as well as on the biology of pathogenic fungi.
Medical mycology as part of medical microbiology is advancing rapidly. Effective therapeutic strategies are already available in chemotherapy and are being further developed. Their application requires reliable laboratory diagnostic techniques, which, in turn, result from mycological basic research. Opportunistic mycoses vary greatly in their clinical and pathological symptoms, because the underlying disease of a patient at risk decisively determines their symptomatology and progress. The journal Mycoses is therefore of interest to scientists in fundamental mycological research, mycological laboratory diagnosticians and clinicians interested in fungal infections.
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