文献类型： 外文期刊

作者： Li, Yinghong ¹ ; Zhang, Hu ³ ; Meng, Tingting ¹ ; Zhou, Yuqin ⁴ ; Zhou, Beilei ² ; Du, Shihan ⁴ ; Yuan, Hong ¹ ; Hu, Fuqiang ¹ ;

作者机构： 1.Zhejiang Univ, Coll Pharmaceut Sci, 866 Yuhangtang Rd, Hangzhou 310058, Peoples R China

2.Zhejiang Inst Food & Drug Control, NMPA Key Lab Testing & Warning Pharmceut Microbiol, Zhejiang Key Lab Biopharmaceut Contact Mat, 325 Pingle St, Hangzhou 310052, Peoples R China

3.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, 198 Shiqiao Rd, Hangzhou 310021, Peoples R China

4.China Pharmaceut Univ, Sch Pharm, 639 Longmian Ave, Nanjing 211198, Peoples R China

关键词： nanostructured lipid carriers; difenoconazole; preparation; antifungal effect; zebrafish; toxicity

期刊名称：PHARMACEUTICALS （ 影响因子：4.8； 五年影响因子：4.9 ）

ISSN：

年卷期： 2025 年 18 卷 6 期

页码：

收录情况： SCI

摘要： Background/Objectives: Difenoconazole (DFC) is a broad-spectrum fungicide. However, its application is limited due to poor aqueous solubility. Drugs with low solubility can be better absorbed using nanostructured lipid carriers (NLCs). Hence, the application of DFC in an NLC delivery system is proposed. Methods: Difenoconazole-loaded nanostructured lipid carriers (DFC-NLCs) with different solid-liquid lipid ratios were prepared by solvent diffusion method. Key physicochemical parameters, including particle diameter, surface charge (zeta potential), drug encapsulation efficiency, and morphological characteristics, were systematically characterized. Using Rhizoctonia solani (R. solani) as the model strain, inhibitory efficiency of DFC-NLC dispersion was compared with that of commercial dosage forms, such as 25% DFC emulsifiable concentrate (DFC-EC) and 40% DFC suspension concentrate (DFC-SC). Additionally, uptakes of DFC-NLC dispersions in R. solani were further observed by fluorescence probe technology. The safety profiles of DFC-NLCs and commercial dosage forms were evaluated using zebrafish as the model organism. Acute toxicity studies were conducted to determine the maximum non-lethal concentration (MNLC) and 10% lethal concentration (LC10). Developmental toxicity studies were performed to observe toxic phenotypes. Results: DFC-NLC dispersions were in the nanometer range (approximate to 200 nm) with high zeta potential, spherical in shape with encapsulation efficiency 69.1 +/- 1.8%similar to 95.0 +/- 2.6%, and drug loading 7.1 +/- 0.3%similar to 9.7 +/- 0.6% determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Compared with commercial dosage forms, the antifungal effect of the DFC-NLC on R. solani was significantly improved in in vitro antibacterial experiments (p < 0.05). The 50% effective concentration (EC50) values were 0.107 mg.L-1 (DFC-NLC), 0.211 mg.L-1 (DFC-EC), and 0.321 mg.L-1 (DFC-SC), respectively. The uptakes of FITC-labeled DFC-NLC demonstrated that an NLC was appropriate to deliver DFC into pathogen to enhance the target effect. In safety assessment studies, DFC-NLCs exhibited a superior safety profile compared with commercial formulations (p < 0.05). Conclusions: This study investigates the feasibility of NLCs as delivery systems for poorly water-soluble fungicides, demonstrating their ability to enhance antifungal efficacy and reduce environmental risks.