白蛋白纳米粒的制备及内耳跨膜给药的初步研究 |
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引用本文: | 于湛,于敏,周志敏,张之宝,杜博,张哲,熊青青,孙建军. 白蛋白纳米粒的制备及内耳跨膜给药的初步研究[J]. 国际生物医学工程杂志, 2013, 0(6): 324-327,343,I0008 |
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作者姓名: | 于湛 于敏 周志敏 张之宝 杜博 张哲 熊青青 孙建军 |
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作者单位: | [1]海军总医院全军耳鼻咽喉中心,北京100037 [2]第二炮兵总医院耳鼻喉科,北京100088 [3]中国医科大学卫生部细胞生物学重点实验室医学细胞生物学教育部重点实验室细胞生物学教研室,沈阳110001 [4]中国医学科学院北京协和医学院生物医学工程研究所,天津300192 |
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基金项目: | 国家自然科学基金面上项目(81170904,81100723) |
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摘 要: | 目的 目前在临床上国内外尚无对内耳病局部用药的缓释剂,本研究旨在探讨能否将白蛋白纳米粒载体材料作为鼓室跨膜给药缓释剂.方法 采用去溶剂化法制备空白白蛋白纳米粒并进行系统表征和细胞毒性评价.为便于观察,选取一种红色荧光染料即罗丹明B(RhB)作为模型药物,以物理吸附方式与空白白蛋白纳米粒结合形成载药白蛋白纳米粒,测定其载药量、包封率及体外药物释放曲线,同时采用小动物活体成像技术观察其注入豚鼠听泡内跨圆窗膜转运扩散情况.结果 制备的白蛋白纳米粒为实心球形,表面光滑,平均粒径大小为476 nm,Zeta电位为15.4 mV.体外药物释放结果表明,该纳米粒具有缓释效果.经戊二醛交联固定的白蛋白纳米粒具有一定的细胞毒性;而经热变性处理的白蛋白纳米粒具有较好的细胞相容性.小动物活体成像实验可以看到RhB在听泡内滞留扩散,而后经解剖观察,证明白蛋白纳米粒可在圆窗膜表面附着并穿越圆窗膜实现跨膜向耳蜗内转运.结论 制备的白蛋白纳米粒结构完整,制备方法简单、无毒性,可以很好地包载药物并具有缓释功能,为进一步制备可注射跨圆窗膜定向缓释纳米凝胶奠定了坚实的基础.
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关 键 词: | 牛血清白蛋白 纳米粒 缓释载体 圆窗膜 内耳 |
Albumin nanoparticle as controlled release carrier for local drug delivery to the inner ear |
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Affiliation: | YU Zhan,YU Min ZHOU Zhi-min ZHANG Zhi-bao DU Bo ZHANG Zhe XIONG Qing-qing( 1.Center of Otorhinolaryngology,PLA Naval General Hospital, Beijing 100037; Department of Otorhinolaryngology, General Hospital of the Second Artillery of PLA, Beijing 100088, China;) |
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Abstract: | Objective To study the clinical application of local drug control-release,modified bovine serum albumin (BSA) nanoparticles was used as controlled release carrier for local drug delivery to the inner ear.Methods Modified BSA nanoparticles,with or without Rhodamine B (RhB),were prepared by improved desolvation method and be confirmed by electron microscope and particle size analyzer.Drug loading,encapsulation efficiency and drug release were analyzed.L929 cells were used for cell biocompatibility assay.Nanoparticles with RhB was used for in vivo imaging to investigate the penetration of particles into the round window membrane (RWM).Results The BSA nanoparticles were smooth-surfaced solid-spheres with average diameter of 476 nm.The Zetapotential of blank nanoparticle was 15.4 mV.RhB,a model drug,was proved to be adsorbed on the nanoparticles and to be release control.Glutaraldehyde cross-linked BSA nanoparticles had certain cytotoxicity,while heat denatured BSA nanoparticles had good cell compatibility.Nanoparticles with RhB was proved to be adsorbed on and penetrated through the RWM.Conclusion The nanoparticles have complete structure and carry drug well for control-release.The preparation is simple and non-toxic.The outcome provides the basis for the study of injectable cross RWM control-release nanogel. |
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Keywords: | Bovine serum albumin Nanoparticle Controlled release carrier, Round window membrane Inner ear |
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