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离心铸造法制备用于透皮提取和给药的微孔无机微针。

Fabrication of microporous inorganic microneedles by centrifugal casting method for transdermal extraction and delivery.

机构信息

Department of Materials Science and Engineering, Faculty of Technology and Engineering, Imam Khomeini International University (IKIU), Qazvin, Iran.

Department of Materials Science and Engineering, Faculty of Technology and Engineering, Imam Khomeini International University (IKIU), Qazvin, Iran.

出版信息

Int J Pharm. 2019 Mar 10;558:299-310. doi: 10.1016/j.ijpharm.2018.12.089. Epub 2019 Jan 14.

Abstract

Microneedle patches have been widely used as transdermal transport systems because of their painless and easy application. Marked rigidity, strength, biocompatibility, and physiological stability are unique features of microneedles fabricated from ceramic materials to be used as microneedle patches. However, the conventional ceramic microneedles are typically dense structures with limited free space for biomolecule loading. A facile method is required for fabrication of biocompatible ceramic microneedles with interconnected porosity. Herein, the simple method of centrifugal casting was developed for fabrication of microporous microneedles from alumina suspensions. The slurry or resin-based alumina suspensions were casted into micromolds under centrifugal force, followed by sintering at high temperatures. The effects of particle size, solvent type, binder amount, resin content and sintering temperature on the microstructure and mechanical properties of microneedles were investigated. By optimizing the process parameters, highly porous (up to 60%) microneedles with interconnected micropores (of diameter ∼1-1.5 μm) were produced. The microporous microneedles were biocompatible and mechanically strong for skin penetration. The potential use of the microneedles for transdermal transportation of biomolecules was shown by fast and accurate extraction of glucose from a skin model and efficient loading and fast release of insulin under physiological conditions. The results suggested that the microporous alumina microneedles may serve as molecular transport systems in transdermal biosensing and drug delivery.

摘要

微针贴片因其无痛、易于应用而被广泛用作经皮输送系统。陶瓷材料制成的微针具有明显的刚性、强度、生物相容性和生理稳定性,是微针贴片的独特特征。然而,传统的陶瓷微针通常是致密结构,用于生物分子加载的自由空间有限。需要一种简单的方法来制造具有互连通孔的生物相容性陶瓷微针。本文开发了一种简单的离心铸造方法,用于从氧化铝悬浮液中制造微孔微针。将浆料或基于树脂的氧化铝悬浮液在离心力下浇铸到微模具中,然后在高温下烧结。研究了粒径、溶剂类型、粘结剂用量、树脂含量和烧结温度对微针微观结构和力学性能的影响。通过优化工艺参数,可以制备出具有互连通微孔(直径约为 1-1.5μm)的高多孔(高达 60%)微针。微孔微针具有生物相容性和机械强度,可用于皮肤穿透。通过从皮肤模型中快速准确地提取葡萄糖以及在生理条件下高效加载和快速释放胰岛素,显示了微针在生物分子经皮输送中的潜在用途。结果表明,多孔氧化铝微针可作为经皮生物传感和药物输送中的分子输送系统。

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