Nosratabadi Mohsen, Rahimnia Seyyed Mobin, Barogh Robab Ebrahimi, Abastabar Mahdi, Haghani Iman, Akhtari Javad, Hajheydari Zohreh, Ebrahimnejad Pedram
Department of Laboratory Sciences, Sirjan School of Medical Sciences, Sirjan, Iran.
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Sci Rep. 2024 Dec 28;14(1):30708. doi: 10.1038/s41598-024-79225-1.
Luliconazole (LCZ) is a topical imidazole antifungal agent with broad-spectrum activity. However, LCZ encounters challenges such as low aqueous solubility, skin retention, and penetration, which reduce its dermal bioavailability and hinder its efficacy in drug delivery. The aim of the present study was to formulate, characterize, and evaluate the in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against a panel of resistant fungal strains. The LCZ-NLCs were synthesized using a modified emulsification-solvent evaporation technique. Characterization involved assessing parameters such as poly-dispersity index (PDI), zeta potential, encapsulation efficiency (EE %), Field Emission Scanning Electron Microscopy (FESEM), Differential Scanning Calorimetry (DSC) analysis, and Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR). Furthermore, in vitro drug release experiments, analysis of release kinetics, cytotoxicity assessments, and in vitro antifungal susceptibility tests were performed as part of the study. The findings indicated that LCZ-NLCs displayed nanoscale dimensions, uniform dispersion, and a favorable zeta potential. The encapsulation efficiency of LCZ in NLCs was approximately 90%. FESEM analysis revealed spherical nanoparticles with consistent shape. ATR-FTIR analysis indicated no chemical interaction between LCZ and excipients. In vitro drug release experiments demonstrated that LCZ-NLCs notably improved the drug's dissolution rate. The stability testing confirmed consistent colloidal nanometer ranges in the LCZ-NLCs samples. Additionally, cytotoxicity tests revealed no toxicity within the tested concentration. Moreover, in vitro antifungal susceptibility tests demonstrated potent antifungal activity of LCZ-NLCs against the tested resistant fungal isolates. The study findings suggest that the LCZ-NLCs formulation developed in this research could be a promising topical treatment for superficial fungal infections, especially in cases of resistant infections. However, the study needs further ex vivo and in vivo tests to ensure safety and efficacy.
卢立康唑(LCZ)是一种具有广谱活性的外用咪唑类抗真菌剂。然而,LCZ面临着诸如水溶性低、皮肤滞留性和渗透性等挑战,这些因素降低了其皮肤生物利用度,并阻碍了其在药物递送中的疗效。本研究的目的是制备、表征和评估载卢立康唑纳米结构脂质载体(LCZ-NLCs)对一组耐药真菌菌株的体外抗真菌疗效。采用改良的乳化溶剂蒸发技术合成了LCZ-NLCs。表征涉及评估诸如多分散指数(PDI)、zeta电位、包封率(EE%)、场发射扫描电子显微镜(FESEM)、差示扫描量热法(DSC)分析和衰减全反射傅里叶变换红外光谱(ATR-FTIR)等参数。此外,作为研究的一部分,还进行了体外药物释放实验、释放动力学分析、细胞毒性评估和体外抗真菌药敏试验。研究结果表明,LCZ-NLCs呈现纳米级尺寸、均匀分散且具有良好的zeta电位。LCZ在NLCs中的包封率约为90%。FESEM分析显示具有一致形状的球形纳米颗粒。ATR-FTIR分析表明LCZ与辅料之间无化学相互作用。体外药物释放实验表明,LCZ-NLCs显著提高了药物的溶解速率。稳定性测试证实了LCZ-NLCs样品在一致的胶体纳米范围内。此外,细胞毒性测试显示在测试浓度范围内无毒性。而且,体外抗真菌药敏试验表明LCZ-NLCs对测试的耐药真菌分离株具有强大的抗真菌活性。研究结果表明,本研究中开发的LCZ-NLCs制剂可能是一种有前景的浅表真菌感染局部治疗药物,尤其是在耐药感染的情况下。然而,该研究需要进一步的体外和体内试验以确保安全性和有效性。