Dissolvable microneedles offer an attractive delivery system for transdermal drug and vaccine delivery. They are most commonly formed by filling a microneedle mold with liquid formulation using vacuum or centrifugation to overcome the constraints of surface tension and solution viscosity. Here, we demonstrate a novel microneedle fabrication method employing an atomised spray technique that minimises the effects of the liquid surface tension and viscosity when filling molds. This spray method was successfully used to fabricate dissolvable microneedles (DMN) from a wide range of sugars (trehalose, fructose and raffinose) and polymeric materials (polyvinyl alcohol, polyvinylpyrrolidone, carboxymethylcellulose, hydroxypropylmethylcellulose and sodium alginate). Fabrication by spraying produced microneedles with amorphous content using single sugar compositions. These microneedles displayed sharp tips and had complete fidelity to the master silicon template. Using a method to quantify the consistency of DMN penetration into different skin layers, we demonstrate that the material of construction significantly influenced the extent of skin penetration. We demonstrate that this spraying method can be adapted to produce novel laminate-layered as well as horizontally-layered DMN arrays. To our knowledge, this is the first report documenting the use of an atomising spray, at ambient, mild processing conditions, to create dissolvable microneedle arrays that can possess novel, laminate layering.

译文

可溶性微针为经皮药物和疫苗输送提供了有吸引力的输送系统。它们最常见的形成方法是使用真空或离心方法用液体制剂填充微针模具,以克服表面张力和溶液粘度的限制。在这里,我们展示了一种新颖的微针制造方法,该方法采用雾化喷涂技术,可最大程度地减少填充模具时液体表面张力和粘度的影响。这种喷雾方法已成功地用于从多种糖 (海藻糖,果糖和棉子糖) 和聚合物材料 (聚乙烯醇,聚乙烯吡咯烷酮,羧甲基纤维素,羟丙基甲基纤维素和海藻酸钠) 中制备可溶性微针 (DMN)。使用单糖成分通过喷涂生产的具有无定形含量的微针来制造。这些微针显示出锋利的尖端,并且对主硅模板具有完全的保真度。使用一种方法来量化DMN渗透到不同皮肤层中的一致性,我们证明了建筑材料显着影响皮肤渗透的程度。我们证明了这种喷涂方法可以适用于生产新型的层状和水平层状DMN阵列。据我们所知,这是第一份报告,记录了在环境温和的处理条件下使用雾化喷雾来创建可溶解的微针阵列,该阵列可以具有新颖的层压层。

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