TY - JOUR
T1 - A Double-Blind Randomised Clinical Trial of Terbinafine-Nanostructured Lipid Carriers
T2 - Should We Anticipate This Strategy for Effective Topical Treatment of Onychomycosis?
AU - Parsay, Shima
AU - Saeedi, Majid
AU - Abastabar, Mahdi
AU - Hedayati, Mohammad Taghi
AU - Rahimnia, Seyyed Mobin
AU - Gholizadeh, Nasim
AU - Kazeminejad, Armaghan
AU - Morteza-Semnani, Katayoun
AU - Gashti, Roozbeh Zare
AU - Asare-Addo, Kofi
AU - Moazeni, Maryam
AU - Nokhodchi, Ali
N1 - Funding Information:
Funding: This research was supported by Mazandaran University of Medical Sciences (Sari, Iran) [Grant No. 14985]. This research was supported by Mazandaran University of Medical Sciences (Sari, Iran) [Grant No. 14985]. The authors express their gratitude to the National Institute for Medical Research Development (NIMAD) for their support (Grant No. 4030811).
Funding Information:
This research was supported by Mazandaran University of Medical Sciences (Sari, Iran) [Grant No. 14985]. The authors express their gratitude to the National Institute for Medical Research Development (NIMAD) for their support (Grant No. 4030811).
Publisher Copyright:
© 2025 The Author(s). Mycoses published by Wiley-VCH GmbH.
PY - 2025/6/1
Y1 - 2025/6/1
N2 - 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.
AB - 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.
KW - antifungal susceptibility test
KW - clinical trial
KW - mycological perspective
KW - NLCs
KW - onychomycosis
KW - severity index
KW - TBF-NLC 1% gel
KW - terbinafine
UR - https://www.scopus.com/pages/publications/105008437669
U2 - 10.1111/myc.70076
DO - 10.1111/myc.70076
M3 - Article
C2 - 40525269
AN - SCOPUS:105008437669
SN - 0933-7407
VL - 68
JO - Mycoses
JF - Mycoses
IS - 6
M1 - e70076
ER -
SDG 3 Good Health and Well-being