CN105018339A - 双腔道细胞电阻阻抗芯片 - Google Patents
双腔道细胞电阻阻抗芯片 Download PDFInfo
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- CN105018339A CN105018339A CN201510027940.4A CN201510027940A CN105018339A CN 105018339 A CN105018339 A CN 105018339A CN 201510027940 A CN201510027940 A CN 201510027940A CN 105018339 A CN105018339 A CN 105018339A
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Abstract
本发明公开了双腔道细胞电阻阻抗芯片，它是由细胞腔、给药腔、阻抗传感芯片和皮肤组成。双腔道细胞电阻阻抗芯片的应用将细胞电阻阻抗技术和体外透皮实验紧密结合起来，因此，可以用来研究经皮给药传递系统的体外药效学。
Description
技术领域
本发明涉及到一种双腔道细胞电阻阻抗芯片，应用于药物制剂如液体制剂、片剂、胶囊、滴丸、膜剂、半固体制剂、缓释和控释制剂的体外释放与体外药效学研究。
背景技术
目前，公知的细胞电阻阻抗芯片是单腔道的细胞电阻阻抗芯片，它是一种能够对贴壁生长的细胞的形态进行实时定量检测的芯片。起初，单腔道细胞电阻阻抗芯片主要是基于细胞生物学的应用，应用范围包括细胞的损伤修复、肿瘤细胞的浸润、体外毒理学检测、细胞的趋化迁移、细胞伸展贴壁、细胞层屏障功能、细胞信号转导、流动状态下细胞行为等。随着，细胞传感阻抗传感技术的发展，单腔道阻抗芯片在药物筛选及研发中也得到了广泛的应用。其中主要涉及到药物的药理学及毒理学的研究、新药临床前安全性评价、药物耐药性的研究，以及对某些药物可进行药效学评价。尽管，单腔道细胞电阻阻抗芯片在药学领域中应用广泛，但是，其无法同时模拟与检测药物制剂如液体制剂、片剂、胶囊、滴丸、膜剂、半固体制剂、缓释和控释制剂的体外释放与体外药效学的两个过程。
发明内容
为了克服现有的单腔道芯片无法模拟制剂体外释放过程的这个不足，本发明提供了一种双腔道的细胞电阻阻抗芯片，该芯片不仅能实现实时、定量、非标记和自动化方式检测药物对细胞的影响，而且还可以准确的模拟制剂体外释放过程，真正实现了药物制剂的体外药效学评价。
本发明解决其技术问题所采用的技术方案是：在现有的单腔道芯片基础上，新建一个给药腔道，此腔道要与原有的细胞接种腔道相互对应，实验中待细胞接种生长到平台期时，停止检测，更换培养液后，细胞接种腔上可放置一层透析膜、动物黏膜或无菌皮肤，然后，将给药腔放置于其上，保证给药腔与底部的单腔道芯片紧密镶嵌之后，将所测制剂加入给药腔中，重新开始测量。
本实验新型的有益效果是，双腔道细胞电阻阻抗芯片的应用，可以将细胞电阻阻抗技术和体外释放实验、透皮实验紧以及黏膜渗透实验密结合起来，建立一种灵敏、实时、准确、简易的体外评价制剂的药效学方法。
下面结合附图和实施例对本实验新型进一步说明。
附图说明
图1.双腔道细胞电阻阻抗芯片正视图照片
图2.双腔道细胞电阻阻抗芯片剖视照片
图3.双腔道细胞电阻阻抗芯片实物照片
图4.应用双腔道细胞电阻阻抗芯片评价盐酸米托蒽醌立方液晶和醇质体凝胶电阻与时间的曲线(X±s，n＝3)
具体实施方式
应用双腔道细胞电阻阻抗芯片评价盐酸米托蒽醌立方液晶和醇质体凝胶
图1中，给药腔(1)紧密结合于细胞接种腔(2)，而细胞电阻传感芯片(3)镶嵌在细胞接种腔底部；图2中两腔之间有一层处理过的无菌大鼠腹部皮肤(4)，实验中取100μl的DMEM培养基接种于各个细胞腔中平衡一分钟，分别将8000个cell/300μl黑色素瘤细胞接种于细胞腔中，开始检测阻抗值，培养10h后(达到细胞生长平台期)停止检测，给细胞换液后，将大鼠腹部皮肤放置于细胞腔上，加上给药腔(保证其与细胞腔紧密结合，不能漏液)，将1.5g的DMEM培养基、1.5g的空白醇质体凝胶、1.5g的立方液晶以及1.5的盐酸米托蒽醌立方液晶和1.5g的盐酸米托蒽醌醇质体凝胶加入给药腔后，药物透过皮肤，进入细胞腔，随着药物被细胞的吸收，细胞阻抗值会随着时间出现一定的变化如图4.。
Claims (7)
1.双腔道细胞电阻阻抗芯片在药物制剂的体外药效学研究领域中的应用。
2.如权利要求1所述的双腔道细胞电阻阻抗芯片，其结构分别为细胞接种腔、给药腔、渗透屏障(无菌皮肤、生物黏膜、透析膜)、阻抗传感芯片。
3.如权利要求1所述的药物制剂包括：液体制剂、片剂、胶囊、滴丸、膜剂、半固体制剂、缓释和控释制剂、靶向制剂。
4.如权利要求1所述的体外药效学研究包括模拟药物制剂透过渗透屏障释放到细胞接种腔的过程以及作用于细胞的实验。
5.如权利要求2所述的无菌皮肤，选自大鼠、小鼠、豚鼠、猪以及人的皮肤。
6.如权利要求2所述的生物黏膜有鼻粘膜、眼黏膜、胃粘膜、肠黏膜等取自人或动物的黏膜。
7.如权利要求2所述的透析膜有再生纤维素膜、醋酸纤维膜、合成膜、替代纤维素膜。
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101576523A (zh) * | 2009-06-11 | 2009-11-11 | 上海交通大学 | 利用微电极阵列阻抗生物传感器芯片检测肿瘤细胞的方法 |
| US20110066120A1 (en) * | 2009-09-16 | 2011-03-17 | Samyang Corporation | Transdermal delivery system, method for manufacturing the same, and transdermal delivery method using the system |
| CN102393406A (zh) * | 2011-08-05 | 2012-03-28 | 杭州柯氏生物科技有限公司 | 一种基于细胞学动态信息集成鉴别道地中药材的方法 |
| CN103308564A (zh) * | 2013-06-03 | 2013-09-18 | 拉芳家化股份有限公司 | 一种化妆品活性成分经皮吸收效率的检测方法 |
| CN203798700U (zh) * | 2014-05-02 | 2014-08-27 | 李焕婷 | 药物透皮吸收实验装置 |
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2015
- 2015-01-21 CN CN201510027940.4A patent/CN105018339A/zh active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101576523A (zh) * | 2009-06-11 | 2009-11-11 | 上海交通大学 | 利用微电极阵列阻抗生物传感器芯片检测肿瘤细胞的方法 |
| US20110066120A1 (en) * | 2009-09-16 | 2011-03-17 | Samyang Corporation | Transdermal delivery system, method for manufacturing the same, and transdermal delivery method using the system |
| CN102393406A (zh) * | 2011-08-05 | 2012-03-28 | 杭州柯氏生物科技有限公司 | 一种基于细胞学动态信息集成鉴别道地中药材的方法 |
| CN103308564A (zh) * | 2013-06-03 | 2013-09-18 | 拉芳家化股份有限公司 | 一种化妆品活性成分经皮吸收效率的检测方法 |
| CN203798700U (zh) * | 2014-05-02 | 2014-08-27 | 李焕婷 | 药物透皮吸收实验装置 |
Non-Patent Citations (1)
| Title |
|---|
| 胡晋红: "《皮肤药理学》", 31 January 2008 * |
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Application publication date: 20151104 |