壳聚糖修饰的聚乳酸-羟基乙酸共聚物纳米颗粒在控制释放抗人类免疫缺陷病毒药物传递中的应用  

Application of chitosan-modified poly(lactic-co-glycolic acid)polymericnano carriers on anti-human immuno-deficiency virus drug encapsulation

作　　者：朱晓红[1] 周诗梦 朱晓霞[2] 邹美银[1] Zhu Xiaohong;Zhou Shimeng;Zhu Xiaoxia;Zou Meiyin(Infection Department of Nantong Third Hospital Affiliated to Nantong University,Nantong 226000,China;School of Public Health,Nantong University,Nantong 226007,China)

机构地区：[1]南通大学附属南通第三医院感染二科,南通市226006 [2]南通大学公共卫生学院,南通市226019

出　　处：《中华实验和临床感染病杂志（电子版）》2023年第2期125-132,共8页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：南通市市级科技计划项目(No.MSZ20172);南通市卫生健康委员会科研立项课题(No.MA2019007)。

摘　　要：目的开发抗人类免疫缺陷病毒(HIV)纳米药物递送系统和释放方式,改善抗HIV药物的生物利用度,并减少不良反应。方法通过水油水乳化和蒸发技术,抗病毒药物依非韦伦、替诺福韦酯和拉米夫定(重量比2︰1︰1)与聚乳酸-羟基乙酸共聚物(PLGA)及壳聚糖混合制备PLGA和聚乳酸-羟基乙酸共聚物-壳聚糖(PLGA-CS)载药纳米颗粒。PLGA和PLGA-CS载药纳米颗粒的粒径、多分散性分布指数和ζ-电位等进行表征,应用高效液相色谱(HPLC)探讨PLGA和PLGA-CS药物载量、包封率和药物释放,体外细胞试验分析生物相容性和细胞毒性。结果PLGA-CS和PLGA颗粒粒径均一性好,经CS修饰PLGA-CS粒径由(198.2±2.3)nm增加至(219.8±6.5)nm,且与扫描电子显微镜(SEM)结果一致。经CS修饰后ζ-电位由(-25±1.6)mV增加至(23.5±1.9)mV。抗病毒药物包封效率由49%~52%增加至68%~77%。4℃和25℃下存储2个月PLGA-CS纳米颗粒药物保持量均>90%,提示PLGA-CS载药纳米颗粒稳定性好。PLGA-CS初始暴发性释放减少,24 h内释放不足20%,与PLGA相比PLGA-CS的释放更长久。MTT实验发现,与PLGA-CS共培养的细胞活力均>91.2%,且不依赖纳米颗粒浓度,提示PLGA-CS细胞毒性低生物相容性高。结论PLGA-CS对抗HIV药物封装率高、稳定性好、无毒,且具有持续释放药物和增强药物疗效的优点,这为HIV感染者临床给药提供了一种新思路。Objective To develop a new nano-drug delivery system,to improve bioavailability and reduce adverse effect of antiretroviral drugs for human immunodeficiency virus(HIV).Methods Nanodrug delivery system produced by awater-oil-water emulsion and solvent evaporation technique was prepared by mixing anti-viral drug:efavirenz(EFV),tenofovir(TDF)and lamivudine(LAM)(weight ratio of 2︰1︰1)with poly(lactic-co-glycolic acid)(PLGA)and PLGA-chitosan(PLGA-CS).The drug-loaded nanoparticles were characterized for their particle size,poly-dispersity index andζ-potential.The drug loading,encapsulation efficiency and drug release of PLGA and PLGA-CS nanoparticles were analyzed by high-performance liquid chromatography(HPLC).In vitro,cell viability was performed to evaluate biocompatibility and cytotoxicity.Results Both PLGA-CS and PLGA nanoparticles exhibit good uniformity in particle size.Due to be coated with CS,the particle size of PLGA-CS nanoparticle was increased from(198.2±2.3)nm to(219.8±6.5)nm;theζ-potential was increased from(-25.0±1.6)mV to(23.5±1.9)mV;drug encapsulation efficiency was increased from 49%-52%to 68%-77%.After a 2-month storage at 4℃or 25℃,the drug retention of PLGA-CS nanoparticles remained above 90%.These results confirmed the excellent stability of PLGA-CS nanoparticles.The initial burst release of the antiretroviral drug from PLGA-CS nanoparticles exhibited a significant reduction,with the drug release remaining below 20%within 24 hours.The results in vitro studies pointed to the prolonged antiviral activity of AR-PLGA-CS.The stability of PLGA-CS was better than PLGA.Regardless of the concentration of PLGA-CS nanoparticles,the MTT assay showed that the cell viability was higher than 90%.This result indicated that PLGA-CS nanoparticles have low toxicity and excellent biocompatibility.Conclusions PLGA-CS nanoparticles exhibited high drug encapsulation efficiency,excellent stability,and the capacity of sustained drug release and enhanced therapeutic efficacy.This provides a new way for the cl

关 键 词：获得性免疫缺陷综合征 聚乳酸-羟基乙酸-壳聚糖 抗病毒药物 药物递送载体控制释放 

分 类 号：R512.91[医药卫生—内科学] R711.3[医药卫生—临床医学]