中华超声影像学杂志
中華超聲影像學雜誌
중화초성영상학잡지
CHINESE JOURNAL OF ULTRASONOGRAPHY
2013年
3期
259-262
,共4页
王希%冉海涛%王志刚%宫玉萍%董桂芳
王希%冉海濤%王誌剛%宮玉萍%董桂芳
왕희%염해도%왕지강%궁옥평%동계방
微气泡%纳米技术%表柔比星%迟效制剂
微氣泡%納米技術%錶柔比星%遲效製劑
미기포%납미기술%표유비성%지효제제
Microbubbles%Nanotechnology%Epirubicin%Delayed-action preparations
目的 将包裹阿霉素(ADM)的乳/羟基乙酸共聚物(PLGA)纳米缓释药物微球(ADM-NP)通过共价结合方式连接于带正电氨基脂质超声微泡(MB-NH2)表面,制备包裹ADM的新型载药微泡,并观察其基本理化特性、载药量、包封率、体外缓释特性及显影效果.方法 采用双乳化法,制备ADM-NP,并通过碳二亚胺法活化ADM-NP表面的羧基,在一定条件下,使ADM-NP以共价结合的方式,连接于MB-NH2表面.用光镜观察连接情况、微泡形态并检测其粒径大小.用高效液相色谱法(HPLC)检测其包封率及载药量,观察该新型载药微泡的体外缓释药特性以及对兔VX2肝癌的显像效果.结果 48 h后光镜观察,可见大量ADM-NP连接于MB-NH2表面,呈花环状,分布较为均匀,其平均最大径为(2.68±0.98)μm.该新型载药微泡的载药量为(8.71±0.46)%,包封率为(86.11±6.76)%.两组体外释药均符合Hignch方程,其结果无明显差异性(P>0.05),48 h体外累积释药量达90%以上.经兔耳缘静脉注射该微泡后,兔肝实质明显持续增强,肝癌呈“快进快退”显像表现.结论 采用碳二亚胺法可将ADM-NP通过共价结合方式连接于MB-NH2表面,提高微泡载药量,延长药物的持续作用时间,并且在兔VX2肝癌肿瘤中显影效果好,为采用超声靶向爆破微泡进行药物定位释放技术提供了一种新型高效的载药微泡系统.
目的 將包裹阿黴素(ADM)的乳/羥基乙痠共聚物(PLGA)納米緩釋藥物微毬(ADM-NP)通過共價結閤方式連接于帶正電氨基脂質超聲微泡(MB-NH2)錶麵,製備包裹ADM的新型載藥微泡,併觀察其基本理化特性、載藥量、包封率、體外緩釋特性及顯影效果.方法 採用雙乳化法,製備ADM-NP,併通過碳二亞胺法活化ADM-NP錶麵的羧基,在一定條件下,使ADM-NP以共價結閤的方式,連接于MB-NH2錶麵.用光鏡觀察連接情況、微泡形態併檢測其粒徑大小.用高效液相色譜法(HPLC)檢測其包封率及載藥量,觀察該新型載藥微泡的體外緩釋藥特性以及對兔VX2肝癌的顯像效果.結果 48 h後光鏡觀察,可見大量ADM-NP連接于MB-NH2錶麵,呈花環狀,分佈較為均勻,其平均最大徑為(2.68±0.98)μm.該新型載藥微泡的載藥量為(8.71±0.46)%,包封率為(86.11±6.76)%.兩組體外釋藥均符閤Hignch方程,其結果無明顯差異性(P>0.05),48 h體外纍積釋藥量達90%以上.經兔耳緣靜脈註射該微泡後,兔肝實質明顯持續增彊,肝癌呈“快進快退”顯像錶現.結論 採用碳二亞胺法可將ADM-NP通過共價結閤方式連接于MB-NH2錶麵,提高微泡載藥量,延長藥物的持續作用時間,併且在兔VX2肝癌腫瘤中顯影效果好,為採用超聲靶嚮爆破微泡進行藥物定位釋放技術提供瞭一種新型高效的載藥微泡繫統.
목적 장포과아매소(ADM)적유/간기을산공취물(PLGA)납미완석약물미구(ADM-NP)통과공개결합방식련접우대정전안기지질초성미포(MB-NH2)표면,제비포과ADM적신형재약미포,병관찰기기본이화특성、재약량、포봉솔、체외완석특성급현영효과.방법 채용쌍유화법,제비ADM-NP,병통과탄이아알법활화ADM-NP표면적최기,재일정조건하,사ADM-NP이공개결합적방식,련접우MB-NH2표면.용광경관찰련접정황、미포형태병검측기립경대소.용고효액상색보법(HPLC)검측기포봉솔급재약량,관찰해신형재약미포적체외완석약특성이급대토VX2간암적현상효과.결과 48 h후광경관찰,가견대량ADM-NP련접우MB-NH2표면,정화배상,분포교위균균,기평균최대경위(2.68±0.98)μm.해신형재약미포적재약량위(8.71±0.46)%,포봉솔위(86.11±6.76)%.량조체외석약균부합Hignch방정,기결과무명현차이성(P>0.05),48 h체외루적석약량체90%이상.경토이연정맥주사해미포후,토간실질명현지속증강,간암정“쾌진쾌퇴”현상표현.결론 채용탄이아알법가장ADM-NP통과공개결합방식련접우MB-NH2표면,제고미포재약량,연장약물적지속작용시간,병차재토VX2간암종류중현영효과호,위채용초성파향폭파미포진행약물정위석방기술제공료일충신형고효적재약미포계통.
Objective To combine the active poly lactic co-glycolic acid (PLGA) nanosperes with adriamycin in side (ADM-NP) on the surface of ultrasound micrbubbles in covalent bonding and to prepare a novel drug-loading ultrasound micrbubble,and observe the physicochemical property.To quantify drug encapsulation efficiency and drug-loading amounts and drug-release properties in vitro and the effect of tumor imaging.Methods ADM-NP were prepared with double emulsification method,The surface carboxyl of ADM-NP was activated with carbodiimide method.Amino ultrasound microbubbles (MB-NH2) were prepared with mechanical shaking.The carboxyl of ADM-NP and the MB-NH2 could take place condensation reaction under a certain condition.Light microscope was used to observe the shape and distribution of the novel micrbubble.High performance liquid chromatography (HPLC) was used to quantify drug encapsulation efficiency and drug loading amounts.This novel microbubbles were put in 2 dialysis bag to observe the releasing properties of ADM in vitro,and one of the bag was using low frequency ultrasound irradiation for 120 s.The effect of tumor imaging using this novel microbubble was observed.Results After 48 hours,a number of ADM-NP attacted to the MB-NH2 like a gar land.Determination of entrapment efficiency and drug loading of it by HPLC weare (86.11 ± 6.76)% and (8.71 ± 0.46)%.The sustained release in vitro can last for more than 48 hours.More than 90% of ADM encapsulated in the 2 groups was sustained released for 48 hours.And the release characteristics of the 2 groups in vitro was in accord with Higuchi equation,and no difference was observed in the 2 groups (P >0.05).The tumor showed typical enhancement pattems of "quick wash-in and quick wash-out".Conclusions To combine the nanospheres to the surface of microbubbles with covalent bonding,it could prepare a novel efficient drug-loading microbubbles for a original technique of ultrasound-targeted microbubble destruction(UTMD).