An Lulu, Huang Xiaowen, Zhong Meizhen, Wu Jiaan, Liu Mei, Geng Liqian, Li Yongyong, Wang Xiuli, Yang Lianjuan, Tan Jingwen
Department of Medical Mycology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, 200092, China.
BMC Microbiol. 2025 Aug 4;25(1):477. doi: 10.1186/s12866-025-04230-x.
Despite the widespread use of fluconazole (FLC) in treating Candida infections, the emergence of drug resistance has become an increasing concern. Our earlier studies showing synergism between minocycline (Min) and azoles were limited by Min's high required concentrations exceeding clinically achievable plasma levels. To overcome this limitation, we engineered novel bovine serum albumin (BSA)-encapsulated minocycline nanoparticles (Min-NPs). Then we evaluated the physicochemical properties such as size, potential, particle stability, drug loading and toxicity to make sure their efficacy and safety. Using checkerboard dilution assays, we demonstrated that Min-NPs significantly enhanced azole activity against Candida species at substantially lower Min concentrations than previously required. For C. albicans and N. glabrata, under a certain concentration of FLC, the concentration of Min-NPs required to reach 50% MIC is less than 4 µg/mL. When tested in a murine model of systemic candidiasis, Min-NPs combined with FLC showed superior therapeutic efficacy compared to conventional Min and FLC combinations. In summary, the modification of this formulation can enhance the synergistic efficacy of Min, thereby enabling its potential application as an adjunctive therapy for drug-resistant Candida infections. Clinical trial number. Not applicable.
尽管氟康唑（FLC）在治疗念珠菌感染方面广泛应用，但耐药性的出现已成为日益关注的问题。我们早期的研究表明米诺环素（Min）与唑类药物之间存在协同作用，但受限于米诺环素所需的高浓度超过了临床可达到的血浆水平。为克服这一限制，我们制备了新型牛血清白蛋白（BSA）包裹的米诺环素纳米颗粒（Min-NPs）。然后我们评估了其物理化学性质，如尺寸、电位、颗粒稳定性、载药量和毒性，以确保其有效性和安全性。通过棋盘稀释试验，我们证明Min-NPs在比以前所需浓度低得多的米诺环素浓度下，能显著增强唑类药物对念珠菌的活性。对于白色念珠菌和光滑念珠菌，在一定浓度的氟康唑下，达到50% MIC所需的Min-NPs浓度小于4 μg/mL。在系统性念珠菌病小鼠模型中进行测试时，与传统的米诺环素和氟康唑联合用药相比，Min-NPs与氟康唑联合用药显示出更好的治疗效果。总之，这种制剂的改良可以增强米诺环素的协同疗效，从而使其有可能作为耐药念珠菌感染的辅助治疗方法应用。临床试验编号。不适用。
