Purpose

To apply a simple and flexible manufacturing technique, two-photon polymerisation (2PP), to the fabrication of microneedle (MN) array templates with high precision and low cost in a short time.

Methods

Seven different MN array templates were produced by 2PP 3D printing, varying needle height (900–1300 μm), shape (conical, pyramidal, cross-shaped and with pedestal), base width (300–500 μm) and interspacing (100–500 μm). Silicone MN array moulds were fabricated from these templates and used to produce dissolving and hydrogel-forming MN arrays. These polymeric MN arrays were evaluated for their insertion in skin models and their ability to deliver model drugs (cabotegravir sodium and ibuprofen sodium) to viable layers of the skin (ex vivo and in vitro) for subsequent controlled release and/or absorption.

Results

The various templates obtained with 2PP 3D printing allowed the reproducible fabrication of multiple MN array moulds. The polymeric MN arrays produced were efficiently inserted into two different skin models, with sharp conical and pyramidal needles showing the highest insertion depth values (64–90% of needle height). These results correlated generally with ex vivo and in vitro drug delivery results, where the same designs showed higher drug delivery rates after 24 h of application.

Conclusion

This work highlights the benefits of using 2PP 3D printing to prototype variable MN array designs in a simple and reproducible manner, for their application in drug delivery.

中文翻译：

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具有多功能设计的微针阵列模板的两光子聚合3D打印：在聚合物药物输送系统开发中的应用。

目的

为了将一种简单而灵活的制造技术，即双光子聚合（2PP），应用于在短时间内以高精度和低成本制造微针（MN）阵列模板。

方法

通过2PP 3D打印，变化的针高（900–1300μm），形状（圆锥形，金字塔形，十字形和带底座），基部宽度（300–500μm）和间距（100–500），可以生产七个不同的MN阵列模板微米）。从这些模板制造有机硅MN阵列模具，并将其用于生产溶解和水凝胶形成的MN阵列。评估了这些聚合物MN阵列在皮肤模型中的插入以及将模型药物（卡博格韦钠和布洛芬钠）递送至皮肤的活体层（离体和体外）以进行随后的受控释放和/或吸收的能力。

结果

通过2PP 3D打印获得的各种模板允许可重复制造多个MN阵列模具。产生的聚合物MN阵列有效地插入了两种不同的皮肤模型中，尖锐的圆锥形和金字塔形针头显示出最高的插入深度值（针头高度的64–90％）。这些结果通常与离体和体外药物递送结果相关，在相同的设计中，应用24小时后显示出较高的药物递送速率。

结论

这项工作强调了使用2PP 3D打印以简单且可重复的方式对可变MN阵列设计进行原型制作的好处，以便将其应用于药物输送。