Craciun Bogdan-Florin, Rosca Irina, Peptanariu Dragos, Pinteala Mariana
Centre of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni", Institute of Macromolecular Chemistry, 41 A Grigore Ghica Voda Alley, Iasi, 700487, Romania.
ChemMedChem. 2025 Jan 2;20(1):e202400432. doi: 10.1002/cmdc.202400432. Epub 2024 Nov 20.
There is an emerging necessity for improved therapies against Candida-related infections, with significant implications for global healthcare. Current antifungal agents, limited in number, target specific pathways, but resistance remains a concern. Flucytosine (5FC) exhibits antifungal activity, particularly against Candida. However, monotherapy efficacy is limited, necessitating combination treatments. Herein, we report PEGylated squalene-based nanocarriers for 5FC loading, aiming to enhance its monotherapy efficacy against Candida strains. The loading of 5FC within micelles was achieved using the ultrasound-assisted solvent evaporation method. The 5FC-loaded micelles, together with non-loaded micelles, were thoroughly characterized and analyzed. STEM and DLS analysis confirmed the core-shell morphology with nanometric dimensions along with improved colloidal stability. The quantification of drug loading efficiency and drug loading capacity was calculated using the UV-Vis technique. The in vitro drug-release studies in simulated physiological conditions showed sustained release within 48 hours. Moreover, the release kinetics calculated using mathematical models showed a Fickian diffusion drug release mechanism in simulated physiological conditions with a slower diffusion rate. The in vitro antifungal activity was tested on Candida albicans, Candida glabrata, and Candida parapsilosis. The results showed improved antifungal activity for the nanotherapeutic and unchanged in vitro toxicity toward normal cells, suggesting promising advancements in 5FC therapy.
针对念珠菌相关感染的改进疗法的需求日益凸显，这对全球医疗保健具有重大意义。目前的抗真菌药物数量有限，靶向特定途径，但耐药性仍然是一个问题。氟胞嘧啶（5FC）具有抗真菌活性，尤其对念珠菌有效。然而，单一疗法的疗效有限，因此需要联合治疗。在此，我们报告了用于负载5FC的聚乙二醇化角鲨烯基纳米载体，旨在提高其对念珠菌菌株的单一疗法疗效。使用超声辅助溶剂蒸发法将5FC负载到胶束中。对负载5FC的胶束和未负载的胶束进行了全面表征和分析。扫描透射电子显微镜（STEM）和动态光散射（DLS）分析证实了具有纳米尺寸的核壳形态以及改善的胶体稳定性。使用紫外可见技术计算药物负载效率和药物负载量。在模拟生理条件下的体外药物释放研究表明，药物在48小时内持续释放。此外，使用数学模型计算的释放动力学表明，在模拟生理条件下，药物释放机制为菲克扩散，扩散速率较慢。对白色念珠菌、光滑念珠菌和近平滑念珠菌进行了体外抗真菌活性测试。结果表明，纳米治疗剂的抗真菌活性有所提高，对正常细胞的体外毒性未变，这表明5FC疗法有了有前景的进展。
