Iontophoretic and microneedle mediated transdermal delivery of glycopyrrolate.
Iontophoretic and microneedle mediated transdermal delivery of glycopyrrolate.
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DOI：
10.3390/pharmaceutics6040663
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发表时间：
2014-12-22
期刊：
影响因子：
5.4
通讯作者：
Banga AK
中科院分区：
文献类型：
--
作者：
Gujjar M;Banga AK
目的：研究离子透渗、可溶性微针及其联合应用在甘罗罗酸透皮给药中的作用。方法：采用全层猪耳皮贴装Franz扩散细胞进行体外渗透实验。离子电泳（0.5 mA/cm2）用Ag/AgCl电极进行4小时。对于微针，在安装前使用三行排列（27针/行）的麦芽糖微针对皮肤进行微孔。通过拍摄钙黄蛋白在孔隙中分布的荧光图像，并使用图像分析工具对图像进行处理，通过测量每个孔隙内和周围的荧光强度来确定孔隙渗透率指数（PPI），从而确定孔隙均匀性。供体室含有500µL 1 mg/mL甘罗酸盐溶液，受体室含有5 mL 50 mM NaCl去离子水。在预定的时间点24小时内采集样品，用高效液相色谱法进行分析。皮肤刺激试验采用人体皮肤三维细胞培养试剂盒进行。MTT法测定细胞活力；活力低于50%被认为是刺激性的。结果：甘罗酸钠被动渗透对照实验24 h平均累积渗透量为24.92±1.77µg/cm2，而微针预处理使其渗透量增加至46.54±6.9µg/cm2。离子透入（158.53±17.50µg/cm2）和离子透入与微针联合（182.43±20.06µg/cm2）相比，单独使用微针和被动使用微针显著增加了递送量。甘罗酸溶液无刺激性，细胞存活率为70.4%±5.03%。结论：离子透入及离子透入联合微针预处理可有效促进甘罗罗酸的透皮给药。glycopyrolate被发现对皮肤无刺激性。
Purpose: The objective of this study was to investigate the use of iontophoresis, soluble microneedles and their combination for the transdermal delivery of glycopyrrolate. Methods: In vitro permeation was tested using full thickness porcine ear skin mounted onto Franz diffusion cells. Iontophoresis (0.5 mA/cm2) was done for 4 h using Ag/AgCl electrodes. For microneedles, three line array (27 needles/line) of maltose microneedles were used to microporate the skin prior to mounting. Pore uniformity was determined by taking fluorescent images of distribution of calcein into pores and processing the images using an image analysis tool, which measured the fluorescent intensity in and around each pore to provide a pore permeability index (PPI). The donor chamber contained 500 µL of a 1 mg/mL solution of glycopyrrolate, and the receptor chamber contained 5 mL of 50 mM NaCl in deionized water. Samples were collected at predetermined time points over a period of 24 h and analyzed by HPLC. Skin irritation testing was performed with a 3D cell culture kit of human skin. MTT assay determined cell viability; viability less than 50% was considered irritant. Results: A control experiment which investigated passive permeation of glycopyrrolate delivered an average cumulative amount of 24.92 ± 1.77 µg/cm2 at 24 h, while microneedle pretreatment increased permeability to 46.54 ± 6.9 µg/cm2. Both iontophoresis (158.53 ± 17.50 µg/cm2) and a combination of iontophoresis and microneedles (182.43 ± 20.06 µg/ cm2) significantly increased delivery compared to passive and microneedles alone. Glycopyrrolate solution was found to be nonirritant with cell viability of 70.4% ± 5.03%. Conclusion: Iontophoresis and a combination of iontophoresis with microneedle pretreatment can be effectively used to enhance the transdermal delivery of glycopyrrolate. Glycopyrrolate was found to be non-irritant to skin.