中国实用眼科杂志
中國實用眼科雜誌
중국실용안과잡지
CHINESE JOURNAL OF PRACTICAL OPHTHALMOLOGY
2013年
1期
86-90
,共5页
刘海芸%朱弼珺%宋正宇%孙晓东%许迅
劉海蕓%硃弼珺%宋正宇%孫曉東%許迅
류해예%주필군%송정우%손효동%허신
超声%造影剂%药物%眼
超聲%造影劑%藥物%眼
초성%조영제%약물%안
Ultrasound%Contrast agent%Medicine%Eye
目的 明确超声微泡结合超声辐照增强贝伐单抗(Avastin)眼内转运的可操作性和有效性.方法 实验室载药Avastin脂质微泡的制备及处方工艺优化,采用高效液相色谱仪测定Avastin浓度、制备标准曲线,混合超声微泡造影剂和Avastin,测定载药脂质微泡的包封率,以及3d内的药物释放情况,检测zeta电位和粒径,并以光镜照相.活体荧光成像检测法观察载Avastin的脂质微泡经超声辐照的眼内穿透的动物实验,制备DiR标记的载Avastin脂质微泡,新西兰白兔8只,分为两组,第一组兔一眼球结膜下注射1.25 mg/0.05 ml DiR标记的载Avastin脂质微泡,另眼对照；第二组兔一眼球结膜下注射1.25 mg/0.05 ml DiR标记的载Avastin脂质微泡,之后予以0.5W/cm2,作用连续1min的超声辐照,另眼对照；术后2d取出兔眼,通过小动物活体成像系统观察眼内房水、虹膜、玻璃体、视网膜脉络膜组织的荧光显示情况.结果 载Avastin脂质微泡的平均粒径为(2526.7±229.53) nm,外形圆整,大小均一；Zeta电位为(2.65±0.09) mv；包封率为(88.65±2.36)％.在4℃条件下1、2、3d Avastin的释放百分率分别为(0.91±0.33)％、(2.41±0.36)％、(7.06±1.64)％.批量制备工艺参数:转速180 rpm、载药温度0℃、载药时间2h.两组兔眼的实验眼的眼内组织与对照眼相比,均显示出明显的荧光,提示经过DiR标记的载药脂质微泡具有穿透组织眼内转运的能力；两组兔眼的实验眼的眼内组织显示荧光相比,接受超声辐照的兔眼比未予超声辐照的要显示出更强的荧光,在玻璃体及虹膜中的分布更多,提示DiR标记的载Avastin的脂质微泡在接受超声辐照后药物在眼球中的分布更多.结论 载Avastin的脂质微泡制备工艺简单,包封率高,稳定性好.载Avastin的脂质微泡结合一定能量的超声辐照后能增加药物的眼内转运.
目的 明確超聲微泡結閤超聲輻照增彊貝伐單抗(Avastin)眼內轉運的可操作性和有效性.方法 實驗室載藥Avastin脂質微泡的製備及處方工藝優化,採用高效液相色譜儀測定Avastin濃度、製備標準麯線,混閤超聲微泡造影劑和Avastin,測定載藥脂質微泡的包封率,以及3d內的藥物釋放情況,檢測zeta電位和粒徑,併以光鏡照相.活體熒光成像檢測法觀察載Avastin的脂質微泡經超聲輻照的眼內穿透的動物實驗,製備DiR標記的載Avastin脂質微泡,新西蘭白兔8隻,分為兩組,第一組兔一眼毬結膜下註射1.25 mg/0.05 ml DiR標記的載Avastin脂質微泡,另眼對照；第二組兔一眼毬結膜下註射1.25 mg/0.05 ml DiR標記的載Avastin脂質微泡,之後予以0.5W/cm2,作用連續1min的超聲輻照,另眼對照；術後2d取齣兔眼,通過小動物活體成像繫統觀察眼內房水、虹膜、玻璃體、視網膜脈絡膜組織的熒光顯示情況.結果 載Avastin脂質微泡的平均粒徑為(2526.7±229.53) nm,外形圓整,大小均一；Zeta電位為(2.65±0.09) mv；包封率為(88.65±2.36)％.在4℃條件下1、2、3d Avastin的釋放百分率分彆為(0.91±0.33)％、(2.41±0.36)％、(7.06±1.64)％.批量製備工藝參數:轉速180 rpm、載藥溫度0℃、載藥時間2h.兩組兔眼的實驗眼的眼內組織與對照眼相比,均顯示齣明顯的熒光,提示經過DiR標記的載藥脂質微泡具有穿透組織眼內轉運的能力；兩組兔眼的實驗眼的眼內組織顯示熒光相比,接受超聲輻照的兔眼比未予超聲輻照的要顯示齣更彊的熒光,在玻璃體及虹膜中的分佈更多,提示DiR標記的載Avastin的脂質微泡在接受超聲輻照後藥物在眼毬中的分佈更多.結論 載Avastin的脂質微泡製備工藝簡單,包封率高,穩定性好.載Avastin的脂質微泡結閤一定能量的超聲輻照後能增加藥物的眼內轉運.
목적 명학초성미포결합초성복조증강패벌단항(Avastin)안내전운적가조작성화유효성.방법 실험실재약Avastin지질미포적제비급처방공예우화,채용고효액상색보의측정Avastin농도、제비표준곡선,혼합초성미포조영제화Avastin,측정재약지질미포적포봉솔,이급3d내적약물석방정황,검측zeta전위화립경,병이광경조상.활체형광성상검측법관찰재Avastin적지질미포경초성복조적안내천투적동물실험,제비DiR표기적재Avastin지질미포,신서란백토8지,분위량조,제일조토일안구결막하주사1.25 mg/0.05 ml DiR표기적재Avastin지질미포,령안대조；제이조토일안구결막하주사1.25 mg/0.05 ml DiR표기적재Avastin지질미포,지후여이0.5W/cm2,작용련속1min적초성복조,령안대조；술후2d취출토안,통과소동물활체성상계통관찰안내방수、홍막、파리체、시망막맥락막조직적형광현시정황.결과 재Avastin지질미포적평균립경위(2526.7±229.53) nm,외형원정,대소균일；Zeta전위위(2.65±0.09) mv；포봉솔위(88.65±2.36)％.재4℃조건하1、2、3d Avastin적석방백분솔분별위(0.91±0.33)％、(2.41±0.36)％、(7.06±1.64)％.비량제비공예삼수:전속180 rpm、재약온도0℃、재약시간2h.량조토안적실험안적안내조직여대조안상비,균현시출명현적형광,제시경과DiR표기적재약지질미포구유천투조직안내전운적능력；량조토안적실험안적안내조직현시형광상비,접수초성복조적토안비미여초성복조적요현시출경강적형광,재파리체급홍막중적분포경다,제시DiR표기적재Avastin적지질미포재접수초성복조후약물재안구중적분포경다.결론 재Avastin적지질미포제비공예간단,포봉솔고,은정성호.재Avastin적지질미포결합일정능량적초성복조후능증가약물적안내전운.
Objective To confirm the operability and effect of ultrasound microbubble combined with ultrasound irradiation system enhance Avastin intraocular delivery.Methods The preparation method of Avastin-loaded microbubbles was studied.High-performance liquid chromatography was used to determine the concentration of Avastin,entrapment efficiency,and drug releasing in 3 days.The optical microscope was used to observe its appearance and distribution.Its mean diameter and zeta potential were detected by Zeta sizer Nano.In vivo fluorescence imaging assay of Avastin intraocular delivery by ultrasound-mediated microbubble was studied.1,1'-dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine Iodide (DiR) marked Avastin-loaded microbubbles were prepared.Eight New Zealand white rabbits were divided into 2 groups,the first group accepted 1.25mg/0.05ml DiR marked Avastin-loaded microbubbles injection subconjunctival in the right eye,the other eye was the control.The second group accepted 1.25mg/0.05ml DiR marked Avastin-loaded microbubbles injection subconjunctival and 0.5W/cm2 ultrasound irradiation continued 1 minute in the right eye,the other eye was the control.Two days after injection,the eyes were removed,and the fluorescence of intraocular tissue was observed.Results The mean diameter of Avastin-loaded microbubbles was 2526.7±229.53 nm,Zeta potential was 2.65±0.09mV,and the drug entrapment efficiency was 88.65±2.36％.4℃,the releasing rate of Avastin on first,second,and third day was (0.91±0.33)％,(2.41±0.36)％,(7.06± 1.64)％,respectively.Batch preparation process parameters:speed of 180rpm,the drug loading temperature 0℃,the drug loading time 2h.The fluorescence of intraocular tissue in 8 right eyes were significantly strong than control eyes.The fluorescence of intraocular tissue in group 2 eyes were obviously strong than group 1,especially in vitreous body and iris.Conclusion Preparation of Avastin-loaded microbubbles is feasible,with the high drug entrapment efficiency and stability.Ultrasound-mediated delivery system can enhance the intraocular delivery of Avastin.
