摘要
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1．25mg／0．05mlDiR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1．25mg／0．05mlDiR标记的载Avastin脂质微泡，之后予以0．5W／cm。，作用连续lmin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、3dAvastin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180rpm、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�
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 rnicrobubbles 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 intra- ocular 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 Zea-land white rabbits were divided into 2 groups, the first group accepted 1.25mg/0.05ml DiR marked Avast±n-loaded microbubbles injection subconjunctival in the right eye, the other eye was the control. The second group accepted h25mg/0.05ml DiR marked Avast±n-loaded microbubbles injection subcon- junctival and 0.5W/cm2 ultrasound irradiation continued l minute in the right eye, the other eye was the control. Two days after injection, the eyes were removed, and the fluorescence of intraocular tis- sue 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±C, 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 temper- ature 0℃, the drug loading time 2h. The fluorescence of intraocular tissue in 8 right eyes were sig- nificantly strong than control eyes. The fluorescence of intraocular tissue in group 2 eyes were obvi- ously strong than group 1, especially in vitreous body and iris. Conclusion Preparation of Avas- tin-loaded microbubbles is feasible, with the h
出处
《中国实用眼科杂志》
CSCD
北大核心
2013年第1期86-90,共5页
Chinese Journal of Practical Ophthalmology
基金
973计划子课题（2011CB707506）,上海市科委医学引导类课题（114119a7000）,上海市眼底病重点实验室开放课题基金（07222911）
关键词
超声
造影剂
药物
眼
Ultrasound
Contrast agent
Medicine
Eye
