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多材料 3D 打印可编程和可拉伸口腔贴片用于递送沙奎那韦。

Multi-material 3D printing of programmable and stretchable oromucosal patches for delivery of saquinavir.

机构信息

Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

Department of Health Technology, Technical University of Denmark, Building 423, 2800 Kgs. Lyngby, Denmark.

出版信息

Int J Pharm. 2021 Dec 15;610:121236. doi: 10.1016/j.ijpharm.2021.121236. Epub 2021 Nov 5.

Abstract

Oromucosal patches for drug delivery allow fast onset of action and ability to circumvent hepatic first pass metabolism of drugs. While conventional fabrication methods such as solvent casting or hot melt extrusion are ideal for scalable production of low-cost delivery patches, these methods chiefly allow for simple, homogenous patch designs. As alternative, a multi-material direct-ink-write 3D printing for rapid fabrication of complex oromucosal patches with unique design features was demonstrated in the present study. Specifically, three print-materials: an acidic saquinavir-loaded hydroxypropyl methylcellulose ink, an alkaline effervescent sodium carbonate-loaded ink, and a methyl cellulose backing material were combined in various designs. The CO content and pH of the microenvironment were controlled by adjusting the number of alkaline layers in the patch. Additionally, the rigid and brittle patches were converted to compliant and stretchable patches by implementing mesh-like designs. Our results illustrate how 3D printing can be used for rapid design and fabrication of multifunctional or customized oromucosal patches with tailored dosages and changed drug permeation.

摘要

口腔黏膜贴片可实现药物的快速起效,并能避免药物的肝脏首过代谢。虽然溶剂浇铸或热熔挤出等传统制造方法非常适合于低成本药物输送贴片的规模化生产,但这些方法主要适用于简单、均匀的贴片设计。作为替代方法,本研究中展示了一种多材料直接墨水书写 3D 打印技术,可用于快速制造具有独特设计特征的复杂口腔黏膜贴片。具体来说,三种打印材料:载有酸性沙奎那韦的羟丙基甲基纤维素墨水、碱性泡腾的碳酸钠载药墨水和甲基纤维素背衬材料以各种设计组合在一起。通过调整贴片中碱性层的数量来控制微环境中的 CO 含量和 pH 值。此外,通过实施网状设计,将刚性和脆性贴片转换为顺应性和可拉伸贴片。我们的结果表明,3D 打印如何可用于快速设计和制造具有定制剂量和改变药物渗透特性的多功能或定制口腔黏膜贴片。

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