In this work, we introduce, for the first time, novel hybrid microneedle patches with implantable poly(lactic-co-glycolic acid) (PLGA) tips aligned with hydrogel-forming microneedle bases (HFMB) using a dissolvable material. A model dye, Nile red, and an antifungal drug, amphotericin B, were loaded into the PLGA tips in a controlled manner by multiple castings. Three different types of pre-formed microneedle bases including conventional dissolving baseplates (MN0), HFMB with needle heights of 600 μm (MN6) and HFMB with needle heights of 800 μm (MN8) were investigated. Compared to the conventional dissolving baseplate (MN0)-based PLGA tipped implantable microneedle design, the addition of the pre-formed HFMB (MN8) improved in vitro and ex vivo insertion capacities of the patches, increased ex vivo drug delivery efficiency up to 80% of the loaded drug and speeded up the implantation process to within 1 min. An adhesion test indicated that the hydrogel baseplate used in this study was easier to peel off from the skin than the dissolving baseplate. In vitro release studies demonstrated that the release of amphotericin B from the drug loading PLGA tips lasts for a week. Antifungal tests of the inserted amphotericin B loaded PLGA tips revealed their antifungal effects against Candida albicans. The MN8 did not dissolve, leaving no viscous residue but absorbed water and disintegrated after immersion into water. The hybrid PLGA-tipped microneedle system will be ideal for rapid implantation and sustained release of amphotericin B for dermal fungal infections. This hybrid patch design is a novel promising technology for delivering drug-eluting microimplants into the skin while ensuring easy and complete removal of the HFMB. It could have many potential applications in implantable intradermal drug delivery.

在这项工作中，我们介绍，对于第一次，新颖的混合微针贴片与植入聚（乳酸-共-glycolic酸），使用可溶解材料与形成水凝胶的微针碱基（HFMB）对齐（PLGA）的提示。模型染料尼罗红和抗真菌药物两性霉素 B 通过多次浇铸以受控方式加载到 PLGA 吸头中。研究了三种不同类型的预成型微针底座，包括常规溶解基板 (MN0)、针高度为 600 μm 的 HFMB (MN6) 和针高度为 800 μm (MN8) 的 HFMB。与传统的基于溶解基板 (MN0) 的 PLGA 尖端植入式微针设计相比，添加预成型的 HFMB (MN8) 改善了体外和体外贴剂的插入能力，将体外药物递送效率提高到装载药物的 80%，并将植入过程加快到 1 分钟内。附着力测试表明，本研究中使用的水凝胶基板比溶解基板更容易从皮肤上剥离。体外释放研究表明，两性霉素 B 从载药 PLGA 尖端的释放持续一周。插入的两性霉素 B 负载 PLGA 尖端的抗真菌测试揭示了它们对白色念珠菌的抗真菌作用. MN8不溶解，没有留下粘性残留物，而是吸水并在浸入水中后分解。混合 PLGA 尖头微针系统将非常适合用于皮肤真菌感染的两性霉素 B 的快速植入和持续释放。这种混合贴片设计是一种新的有前途的技术，用于将药物洗脱微植入物输送到皮肤中，同时确保轻松彻底地去除 HFMB。它可能在植入式皮内给药方面有许多潜在的应用。