环孢素A壳聚糖纳米粒修饰人工晶状体表面的实验研究
배포소A각취당납미립수식인공정상체표면적실험연구
Experimental study on surface modification of intraocular lens by cyclosporine A-loaded chitosan nanoparticle
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    中华实验眼科杂志 중화실험안과잡지
    CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
    2013年 10期 935-939 ,共5页

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    壳聚糖纳米粒%环孢素A%人工晶状体%离子交联法%表面修饰 殼聚糖納米粒%環孢素A%人工晶狀體%離子交聯法%錶麵脩飾
    각취당납미립%배포소A%인공정상체%리자교련법%표면수식
    Chitosan nanoparticle%Cyclosporin A%Intraocular lens%Ionic gelation%Surface modification
    背景 白内障囊外摘出术后发生后囊膜混浊(PCO)是影响患者术后视力的主要原因,目前探讨药物的局部应用来预防PCO已成为研究的热点. 目的 采用离子交联法制备环孢素A壳聚糖纳米粒(CyA-CS-NP),观察其体外释放性能及修饰聚甲基丙烯酸甲酯(PMMA)人工晶状体(IOL)边缘的可行性.方法 制备壳聚糖纳米粒(CS-NP)和CyA-CS-NP,用透射电子显微镜观察纳米粒的形态学特征,用高效液相色谱仪(HPLC)观察纳米粒的形态学特征、载药率、包载率及体外释药性能,并测定CyA-CS-NP修饰后IOL表面CyA的含量.CyA-CS-NP修饰经等离子处理PMMA IOL边缘,并用扫描电子显微镜观察IOL的表面特征.用X射线光电子能谱仪(XPS)检测单纯等离子体处理过的IOL和CyA-CS-NP修饰过的IOL边缘,分析并比较两种修饰方法处理的IOL表面的元素组成及化学键类型改变；用后焦距法和分光光度计分别测定IOL的屈光度和波长360～ 490 nm内的透光率,并参照ISO/CD 11979-2进行有效分辨率测试,检测IOL的光学性能；参照国际标准ISO/CD 11979-3测定IOL襻抗疲劳度测试. 结果 CS-NP和CyA-CS-NP呈单分散性、形状规则的类球形,粒径分别为(158±18)nm和(219±29) nm.CyA-CS-NP的平均包载率为64.2％,平均载药率为7.6％.体外缓释实验表明,第1天的快速释放阶段释药量达46.6％,此后为缓释阶段,在第12天时释药量达到77.7％.修饰后的IOL边缘存在CyA-CS-NP涂层,XPS检测显示IOL边缘存在CyA-CS-NP的特定元素及官能团,而等离子体处理的IOL未出现类似元素及官能团.3枚IOL表面负载CyA的平均质量为171.88 μg,修饰后的IOL屈光度、分辨率和透光率分别为(16.64±0.23)D、(90.28±0.25)％及(73.57±0.62)％,与修饰前的(16.62±0.29)D、(90.28±0.21)％及(73.61±0.60)％相比差异均无统计学意义(t=0.381、0.078、2.291,均P＞0.05).IOL襻符合国际标准. 结论 与修饰前相比,经CyA-CS-NP边缘修饰的IOL光学性能和襻抗疲劳强度均无明显变化,符合国际标准,满足IOL的临床使用要求,可能成为眼内缓释给药的理想途径.
    배경 백내장낭외적출술후발생후낭막혼탁(PCO)시영향환자술후시력적주요원인,목전탐토약물적국부응용래예방PCO이성위연구적열점. 목적 채용리자교련법제비배포소A각취당납미립(CyA-CS-NP),관찰기체외석방성능급수식취갑기병희산갑지(PMMA)인공정상체(IOL)변연적가행성.방법 제비각취당납미립(CS-NP)화CyA-CS-NP,용투사전자현미경관찰납미립적형태학특정,용고효액상색보의(HPLC)관찰납미립적형태학특정、재약솔、포재솔급체외석약성능,병측정CyA-CS-NP수식후IOL표면CyA적함량.CyA-CS-NP수식경등리자처리PMMA IOL변연,병용소묘전자현미경관찰IOL적표면특정.용X사선광전자능보의(XPS)검측단순등리자체처리과적IOL화CyA-CS-NP수식과적IOL변연,분석병비교량충수식방법처리적IOL표면적원소조성급화학건류형개변；용후초거법화분광광도계분별측정IOL적굴광도화파장360～ 490 nm내적투광솔,병삼조ISO/CD 11979-2진행유효분변솔측시,검측IOL적광학성능；삼조국제표준ISO/CD 11979-3측정IOL반항피로도측시. 결과 CS-NP화CyA-CS-NP정단분산성、형상규칙적류구형,립경분별위(158±18)nm화(219±29) nm.CyA-CS-NP적평균포재솔위64.2％,평균재약솔위7.6％.체외완석실험표명,제1천적쾌속석방계단석약량체46.6％,차후위완석계단,재제12천시석약량체도77.7％.수식후적IOL변연존재CyA-CS-NP도층,XPS검측현시IOL변연존재CyA-CS-NP적특정원소급관능단,이등리자체처리적IOL미출현유사원소급관능단.3매IOL표면부재CyA적평균질량위171.88 μg,수식후적IOL굴광도、분변솔화투광솔분별위(16.64±0.23)D、(90.28±0.25)％급(73.57±0.62)％,여수식전적(16.62±0.29)D、(90.28±0.21)％급(73.61±0.60)％상비차이균무통계학의의(t=0.381、0.078、2.291,균P＞0.05).IOL반부합국제표준. 결론 여수식전상비,경CyA-CS-NP변연수식적IOL광학성능화반항피로강도균무명현변화,부합국제표준,만족IOL적림상사용요구,가능성위안내완석급약적이상도경.
    Background Posterior capsular opacification (PCO) following cataract extracapsular extraction is a major cause of the reduction of visual acuity.Topical administration of eye drops is a research hotspot for the prevention of PCO.Objective This study was to evaluate the release of cyclosporine A-loaded chitosan nanoparticles (CyA-CS-NP) by ionic gelation in vitro and its feasibility of modification of the surface of polymethylmethacrylate intraocular lens (PMMA IOL) with CyA-CS-NP.Methods The CS-NP and CyA-CS-NP were prepared by ionic gelation of CS with sodium tripolyphosphate.The characteristics of CS-NP,such as the appearance and mean size,and drug entrapment efficient (EE),loading capacity (LC),and the drug release were studied ; the CyA content on the IOL surface was detected by high performance liquid chromatography (HPLC).The IOL surface modified with CyA-CS-NP was observed by scanning electron microscope and X-ray photoelectron spectroscopy technique (XPS),the changes of elements and chemical bond types between simple plasma processed IOL and CyA-CS-NP modified IOL were analyzed.The transmittance at the wavelength of 360-490 nm and refraction of IOL were detected using back focal length method and spectrophotometer,and the effective resolution of IOL was evaluated according to the instruction of ISO/CD 11979-2.Loops anti fatigue test of IOL referred to the criteria of ISO/CD 11979-3.Results The CS-NP and CyA-CS-NP showed monodisperse,uniform appearance similar to spherical shape with a mean size of (158±18) nm and (219±29) nm,respectively.The CyA-CS-NP had high CyA association efficiency and loading capacity (64.2％ and 7.6％).In vitro release study revealed a fast release on the first day followed by a increased drug release during an 11-day following up.The sustained release was approximately 46.6％ at day 1 and 77.7％ at day 12,respectively.The surface of IOLs with cling film was smooth without CS-NP;while the edge of IOLs appeared a layer of CyA-CS-NP after modification.XPS analysis displayed some elements such as phosphonium,CNH2 and O =CN that appeared on the modified surface,indicating that CyA-CS-NP existed on the surface of IOLs edge.The mean quality of CyA on three IOLs surface after modification was 171.88 μg.The diopter,distinguishing ability and transmittance of modified IOL were (16.64±0.23) D,(90.28 ± 0.25) ％ and (73.57 ±0.62) ％,and those of unmodified IOL were (16.62±0.29) D,(90.28±0.21) ％,(73.61±0.60)％,without significant differences between them (t =0.381,0.078,2.291,all at P ＞ 0.05).The antifatigue ability of loops complied with the criteria of ISO/CD 11979-3.Conclusions The optical property and antifatigue ability of loops of the edge-modified IOLs by CyA-CS-NP reach the normal standard and meet the requirement of clinic application.The edge-modified IOLs by CyA-CS-NP can be a delivery system for intraocular drug release.
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