Ajalloueian Fatemeh, Eklund Thamdrup Lasse Højlund, Mazzoni Chiara, Petersen Ritika Singh, Keller Stephan Sylvest, Boisen Anja
Department of Health Technology, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark.
The Danish National Research Foundation and Villum Foundation's Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Ørsted Plads, 2800, Kgs. Lyngby, Denmark.
Heliyon. 2024 May 8;10(10):e30844. doi: 10.1016/j.heliyon.2024.e30844. eCollection 2024 May 30.
Recent advances in the use of nano- and microparticles in drug delivery, cell therapy, and tissue engineering have led to increasing attention towards nanostructured microparticulate formulations for maximum benefit from both nano- and micron sized features. Scalable manufacturing of monodisperse nanostructured microparticles with tunable size, shape, content, and release rate remains a big challenge. Current technology, mainly comprises complex multi-step chemical procedures with limited control over these aspects. Here, we demonstrate a novel technique for high-yield fabrication of monodisperse monolayer and multilayer nanofibrous microparticles (MoNami and MuNaMi respectively). The fabrication procedure includes sequential electrospinning followed by micro-cutting at room temperature and transfer of particles for collection. The big advantage of the introduced technique is the potential to apply several polymer-drug combinations forming multilayer microparticles enjoying extracellular matrix (ECM)-mimicking architecture with tunable release profile. We demonstrate the fabrication and study the factors affecting the final three-dimensional structure. A model drug is encapsulated into a three-layer sheet (PLGA-pullulan-PLGA), and we demonstrate how the release profile changes from burst to sustain by simply cutting particles out of the electrospun sheet. We believe our fabrication method offers a unique and facile platform for realizing advanced microparticles for oral drug delivery applications.
纳米和微粒在药物递送、细胞治疗及组织工程中的应用取得的最新进展，已使人们越来越关注纳米结构微粒制剂，以便从纳米和微米尺寸的特性中获得最大益处。可扩展制造具有可调尺寸、形状、含量和释放速率的单分散纳米结构微粒仍然是一项巨大挑战。当前技术主要包括复杂的多步化学程序，对这些方面的控制有限。在此，我们展示了一种高产率制造单分散单层和多层纳米纤维微粒（分别为MoNami和MuNaMi）的新技术。制造过程包括在室温下依次进行静电纺丝，然后进行微切割，并转移颗粒进行收集。所引入技术的一大优势在于，有可能应用多种聚合物-药物组合来形成多层微粒，这些微粒具有模仿细胞外基质（ECM）的结构，且释放曲线可调。我们展示了其制造过程，并研究了影响最终三维结构的因素。将一种模型药物封装到三层片材（聚乳酸-乙醇酸共聚物-支链淀粉-聚乳酸-乙醇酸共聚物）中，我们展示了通过简单地从静电纺丝片材上切割颗粒，释放曲线如何从突释转变为缓释。我们相信，我们的制造方法为实现用于口服药物递送应用的先进微粒提供了一个独特且简便的平台。
