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

Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application.
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DOI:
10.1007/s11095-013-1137-x
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发表时间:
2014-01
影响因子:
3.7
通讯作者:
Ozdoganlar, O. Burak
Ozdoganlar, O. Burak
中科院分区:
医学3区
文献类型:
--
作者:
Bediz, Bekir;Korkmaz, Emrullah;Khilwani, Rakesh;Donahue, Cara;Erdos, Geza;Falo, Louis D., Jr.;Ozdoganlar, O. Burak

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设计和评估一种新的基于微机械加工的方法,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),用于干燥递送至皮肤微环境。其目的是描述新的制造方法,以评估几何和材料的能力,以及该方法的再现性,并证明制造的MNAs在提供生物活性分子的有效性。使用微铣削创建精确的母模。微模塑用于从母模创建弹性体生产模具。然后使用旋转浇铸方法制备可溶解的MNAs。评价了具有不同几何形状的制造的MNA的再现性。从不同的材料制造的MNAs,以显示材料的能力。测试了具有嵌入的生物活性组分的MNAs在人和小鼠皮肤上的功能。使用我们的方法可重复地创建具有不同几何形状和来自羧甲基纤维素、聚乙烯吡咯烷酮和麦芽糖糊精的MNAs。MNAs成功地穿透皮肤,将其生物活性货物精确地递送到皮肤并诱导小鼠的特异性免疫。我们证明了新的制造方法能够以不同的几何形状和不同的材料可重复地创建可溶解的MNAs。我们还展示了MNAs在体外和体内将生物分子精确和特异性递送到皮肤微环境中的应用。
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. 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. 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. 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.
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