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可溶解微针阵列用于生物制剂的皮内递药:制备与应用。

Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application.

机构信息

Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA.

出版信息

Pharm Res. 2014 Jan;31(1):117-35. doi: 10.1007/s11095-013-1137-x. Epub 2013 Aug 1.

Abstract

PURPOSE

Design and evaluate a new micro-machining based approach for fabricating dissolvable microneedle arrays (MNAs) with diverse geometries and from different materials for dry delivery to skin microenvironments. The aims are to describe the new fabrication method, to evaluate geometric and material capability as well as reproducibility of the method, and to demonstrate the effectiveness of fabricated MNAs in delivering bioactive molecules.

METHODS

Precise master molds were created using micromilling. Micromolding was used to create elastomer production molds from master molds. The dissolvable MNAs were then fabricated using the spin-casting method. Fabricated MNAs with different geometries were evaluated for reproducibility. MNAs from different materials were fabricated to show material capability. MNAs with embedded bioactive components were tested for functionality on human and mice skin.

RESULTS

MNAs with different geometries and from carboxymethyl cellulose, polyvinyl pyrrolidone and maltodextrin were created reproducibly using our method. MNAs successfully pierce the skin, precisely deliver their bioactive cargo to skin and induce specific immunity in mice.

CONCLUSIONS

We demonstrated that the new fabrication approach enables creating dissolvable MNAs with diverse geometries and from different materials reproducibly. We also demonstrated the application of MNAs for precise and specific delivery of biomolecules to skin microenvironments in vitro and in vivo.

摘要

目的

设计并评估一种新的基于微加工的方法,用于制造具有不同几何形状和不同材料的可溶解微针阵列(MNAs),以便进行干式递送至皮肤微环境。目的是描述新的制造方法,评估该方法的几何形状和材料性能以及可重复性,并展示所制造的 MNAs 在递送至生物活性分子方面的有效性。

方法

使用微铣削创建精确的主模具。使用微成型从主模具制作弹性体生产模具。然后使用旋转浇铸法制造可溶解的 MNAs。评估不同几何形状的制造 MNAs 的重现性。制造不同材料的 MNAs 以展示材料性能。测试了嵌入生物活性成分的 MNAs 在人皮肤和小鼠皮肤的功能。

结果

使用我们的方法,可以可重复地制造具有不同几何形状和由羧甲基纤维素、聚乙烯吡咯烷酮和麦芽糊精制成的 MNAs。MNAs 成功地刺穿皮肤,将其生物活性货物精确递送至皮肤,并在小鼠中诱导特异性免疫。

结论

我们证明了新的制造方法能够可重复地制造具有不同几何形状和不同材料的可溶解 MNAs。我们还证明了 MNAs 在体外和体内精确和特异性递送至皮肤微环境中的生物分子的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b6b/3898465/c520075ecce6/nihms511811f1.jpg

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