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微针辅助基因枪介导的微颗粒递药:应用于皮肤模拟琼脂糖凝胶的实验。

Microneedle assisted micro-particle delivery from gene guns: experiments using skin-mimicking agarose gel.

机构信息

Department of Chemical Engineering, Loughborough University, Loughborough, LE113TU, UK.

出版信息

J Pharm Sci. 2014 Feb;103(2):613-27. doi: 10.1002/jps.23835. Epub 2014 Jan 7.

DOI:10.1002/jps.23835
PMID:24399616
Abstract

A set of laboratory experiments has been carried out to determine if micro-needles (MNs) can enhance penetration depths of high-speed micro-particles delivered by a type of gene gun. The micro-particles were fired into a model target material, agarose gel, which was prepared to mimic the viscoelastic properties of porcine skin. The agarose gel was chosen as a model target as it can be prepared as a homogeneous and transparent medium with controllable and reproducible properties allowing accurate determination of penetration depths. Insertions of various MNs into gels have been analysed to show that the length of the holes increases with an increase in the agarose concentration. The penetration depths of micro-particle were analysed in relation to a number of variables, namely the operating pressure, the particle size, the size of a mesh used for particle separation and the MN dimensions. The results suggest that the penetration depths increase with an increase of the mesh pore size, because of the passage of large agglomerates. As these particles seem to damage the target surface, then smaller mesh sizes are recommended; here, a mesh with a pore size of 178 μm was used for the majority of the experiments. The operating pressure provides a positive effect on the penetration depth, that is it increases as pressure is increased. Further, as expected, an application of MNs maximises the micro-particle penetration depth. The maximum penetration depth is found to increase as the lengths of the MNs increase, for example it is found to be 1272 ± 42, 1009 ± 49 and 656 ± 85 μm at 4.5 bar pressure for spherical micro-particles of 18 ± 7 μm diameter when we used MNs of 1500, 1200 and 750 μm length, respectively.

摘要

已经进行了一系列实验室实验,以确定微针(MN)是否可以增加高速微颗粒通过基因枪输送的穿透深度。将微颗粒发射到模型靶材琼脂糖凝胶中,该凝胶旨在模拟猪皮的粘弹性。选择琼脂糖凝胶作为模型靶材,因为它可以制备成具有均匀透明的介质,具有可控和可重复的性质,允许准确确定穿透深度。分析了各种 MN 插入凝胶中的情况,表明孔的长度随着琼脂糖浓度的增加而增加。分析了微颗粒的穿透深度与多个变量的关系,即操作压力、颗粒尺寸、用于颗粒分离的网眼尺寸和 MN 尺寸。结果表明,穿透深度随着网眼孔径的增加而增加,因为大团聚体的通过。由于这些颗粒似乎会损坏靶表面,因此建议使用较小的网眼尺寸;在此,大多数实验都使用孔径为 178 μm 的网眼。操作压力对穿透深度有积极影响,即随着压力的增加而增加。此外,正如预期的那样,MN 的应用使微颗粒的穿透深度最大化。发现最大穿透深度随着 MN 长度的增加而增加,例如,当我们使用长度分别为 1500、1200 和 750 μm 的 MN 时,在 4.5 巴的压力下,18 ± 7 μm 直径的球形微颗粒的最大穿透深度分别为 1272 ± 42、1009 ± 49 和 656 ± 85 μm。

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