Dianati Haniyeh, Esmailpour Payam, Dilmaghani Azita, Shayanfar Ali, Hashemzadeh Nastaran, Baradaran Behzad, Hallaj-Nezhadi Somayeh
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Braz J Microbiol. 2025 Aug 22. doi: 10.1007/s42770-025-01720-y.
Flucytosine (FC) is currently used as an antifungal drug for the treatment of infectious diseases. However, due to the development of drug resistance, the monotherapy of FC is limited. Recently, nanoliposomes have been studied as promising approaches to overcome microbial resistance. In this study, we encapsulate FC in the nanoliposomes and investigate their physicochemical properties as well as antifungal activities against Candida glabrata and Candida albicans in-vitro. Various liposomal formulations of FC were prepared based on the modified freeze-drying of a monophase solution method. The nanoliposomes were characterized in terms of size, zeta potential, transmission electron microscopy image, encapsulation efficiency, stability, release, crystallography, and cytotoxicity. Also, the minimum inhibitory concentration and minimum fungicidal concentration were determined against C. glabrata and C. albicans. The size and zeta potential of the selected nanoliposomes were 147.33 ± 23.25 nm and - 31.20 ± 9.05 mV, respectively. Encapsulation efficiency was 46.7 ± 7.5% in the selected formulation. TEM results revealed that the nanoliposomes were nano-sized and spherical. Release results indicated that the nanoliposomes had a slow-release rate of FC. The fungal eradication of nanoliposomal FC was at least two times higher than that of the free drug for C. glabrata and C. albicans. Cytotoxicity studies demonstrated no significant toxicity at effective concentrations of nanoliposomal FC. The stability of the nano-formulation was temperature-dependent, and the refrigerator showed the best condition for long-term storage. Nanoliposomal FC prepared using the modified freeze-drying of a monophase solution method seems promising and may be used to overcome the fungal resistance relative to FC.
氟胞嘧啶（FC）目前用作治疗传染病的抗真菌药物。然而，由于耐药性的发展，FC的单一疗法受到限制。最近，纳米脂质体已被研究作为克服微生物耐药性的有前景的方法。在本研究中，我们将FC包裹在纳米脂质体中，并研究其物理化学性质以及对光滑念珠菌和白色念珠菌的体外抗真菌活性。基于单相溶液法的改良冷冻干燥制备了各种FC脂质体制剂。对纳米脂质体的大小、zeta电位、透射电子显微镜图像、包封效率、稳定性、释放、晶体学和细胞毒性进行了表征。此外，还测定了对光滑念珠菌和白色念珠菌的最低抑菌浓度和最低杀菌浓度。所选纳米脂质体的大小和zeta电位分别为147.33±23.25nm和-31.20±9.05mV。所选制剂的包封效率为46.7±7.5%。透射电镜结果显示纳米脂质体为纳米尺寸且呈球形。释放结果表明纳米脂质体对FC具有缓释速率。纳米脂质体FC对光滑念珠菌和白色念珠菌的真菌根除率至少比游离药物高两倍。细胞毒性研究表明，在纳米脂质体FC的有效浓度下没有明显毒性。纳米制剂的稳定性与温度有关，冰箱显示出最佳的长期储存条件。使用单相溶液法的改良冷冻干燥制备的纳米脂质体FC似乎很有前景，可用于克服相对于FC的真菌耐药性。
