伊曲康唑的新型两亲性壳聚糖纳米抗菌剂的制备及其体外抗白色念珠菌活性  

A new type of itraconazole amphiphilic chitosan preparation of nanometer antibacterial agent and activity against Candida albicans in vitro

作　　者：王曹甘泓 赵冰可 刘政 张建楠[2] 蔡靓羽[2] 邱立朋 WANG-CAO Gan-hong;ZHAO Bing-ke;LIU Zheng;ZHANG Jian-nan;CAI Liang-yu;QIU Li-peng(School of Life Sciences and Health Engineering,Jiangnan University,Wuxi 214122,China;Wuxi Traditional Chinese Medicine Hospital,Wuxi 214071,China)

机构地区：[1]江南大学生命科学与健康工程学院,江苏无锡214122 [2]无锡市中医医院,江苏无锡214071

出　　处：《药学学报》2024年第12期3379-3387,共9页Acta Pharmaceutica Sinica

基　　金：无锡市中医药管理局科技项目(ZYKJ202101)

摘　　要：抗真菌药物自身局限性和严重的耐药性使得药物治疗侵袭性真菌感染(invasive fungal infections,IFIs)面临巨大挑战。伊曲康唑(itraconazole,ITZ)作为临床一线用药,发挥广泛抗真菌活性的同时,依然因其水溶性差、注射剂易造成药物积蓄等引起肝肾毒性和头痛腹痛等不良反应受到限制。因此,开发新型ITZ制剂降低不良反应对真菌感染的治疗极具现实意义。本研究通过酰胺反应和希夫碱反应制备了没食子酸-壳聚糖-肉桂醛(gallic acid-chitosan-cinnamaldehyde,GA-CS-CN)两亲性聚合物,采用超声法制备得到载药纳米粒(GA-CS-CN/ITZ),考察其制剂学性质及体外抗真菌活性效果,并通过细胞毒性实验及体外溶血实验初步评价其生物安全性。研究表明,GA-CS-CN/ITZ呈球型、均一稳定,粒径为239.57±31.37 nm,ITZ包封率为(93.41±1.12)%,48 h时的体外药物累计释放达(62.25±1.88)%,且具有良好的生物安全性。Candida albicans ATCC 10231 (C.albicans)的抗真菌活性结果表明该纳米粒具有最优的抗白色念珠菌效果,可显著增强游离药物的抗真菌活性。本研究设计制备的GA-CS-CN/ITZ具有优良的抗白色念珠菌效果和生物安全性,为治疗白色念珠菌感染提供了新选择,在治疗该真菌感染方面具有良好的应用潜力。The limitations of antifungal drugs and severe drug resistance make the treatment of invasive fungal infections(IFIs) a great challenge.Itraconazole(ITZ),as a clinical first-line drug,has a wide range of antifungal activity,but it is still limited by adverse reactions such as liver and kidney toxicity,headache and abdominal pain due to its poor water solubility and easy to cause drug accumulation by injection.In this study,the amphiphilic polymer gallic acid-chitosan-cinnamaldehyde(GA-CS-CN) was prepared by amide reaction and Schiff-base reaction.The drug-loaded nanoparticles(GA-CS-CN/ITZ) were prepared by ultrasonic method.The properties of nanoparticles formulations and its in vitro antifungal activity were investigated in the study.Studies have shown that GA-CS-CN/ITZ is spherical,homogeneous and stable,and has good biological safety.The average particle size was 239.57 ± 31.37 nm,ITZ encapsulation efficiency was(93.41 ± 1.12)%,and the cumulative drug release was(62.25 ± 1.88)% at 48 h in vitro.The antifungal activity results of Candida albicans ATCC 10231(C.albicans) showed that it had the optimal antifungal effect and could significantly enhance the antifungal activity of free drugs.GA-CS-CN/ITZ prepared in this study has excellent biological safety and anti-C.albicans performance,which provides a new choice for the treatment of C.albicans infection and has good application potential in the treatment of this fungal infection.

关 键 词：伊曲康唑 白色念珠菌感染 纳米技术 壳聚糖 纳米粒 

分 类 号：R943[医药卫生—药剂学]