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用于 3D 打印长效药物输送应用的新型聚酯基热塑性弹性体。

Novel polyester-based thermoplastic elastomers for 3D-printed long-acting drug delivery applications.

机构信息

Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.

Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria.

出版信息

J Control Release. 2021 Jul 10;335:290-305. doi: 10.1016/j.jconrel.2021.05.030. Epub 2021 May 24.

DOI:10.1016/j.jconrel.2021.05.030
PMID:34044092
Abstract

To improve patient compliance and personalised drug delivery, long-acting drug delivery devices (LADDDs), such as implants and inserts, greatly benefit from a customisation in their shape through the emerging 3D-printing technology, since their production usually follows a one-size-fits-most approach. The use of 3D-printing for LADDDs, however, is mainly limited by the shortage of flawlessly 3D-printable, yet biocompatible materials. The present study tackles this issue by introducing a novel, non-biodegradable material, namely a polyester-based thermoplastic elastomer (TPC) - a multi-block copolymer containing alternating semi-crystalline polybutylene terephthalate hard segments and poly-ether-terephthalate amorphous soft segments. Next to a detailed description of the material's 3D-printability by mechanical, rheological and thermal analyses, which was found to be superior to that of conventional polymers (ethylene-vinyl acetates (EVA)), this study establishes the fundamental understandings of the interactions between progesterone (P4) and TPC and drug-releasing properties of TPC for the first time. P4-loaded LADDDs based on TPC, prepared via an elaborated solvent-immersion technique, enable the release of P4 at pharmacologically relevant rates, similar to those of marketed formulations based on EVA and silicones. Additionally, TPC demonstrated an exceptional 3D-printability for a wide selection of implant sizes and complex geometries.

摘要

为了提高患者的依从性和药物的个性化传递,长效药物输送装置(LADDD),如植入物和插入物,通过新兴的 3D 打印技术在形状上进行定制,从而大大受益,因为它们的生产通常采用一刀切的方法。然而,3D 打印在 LADDD 中的应用主要受到缺乏完美 3D 可打印但生物相容材料的限制。本研究通过引入一种新型的不可生物降解材料,即聚酯基热塑性弹性体(TPC) - 一种含有交替半结晶聚对苯二甲酸丁二醇酯硬段和聚醚对苯二甲酸酯无定形软段的多嵌段共聚物,解决了这个问题。除了通过机械、流变和热分析详细描述材料的 3D 可打印性,发现其优于传统聚合物(乙烯-醋酸乙烯酯(EVA))外,本研究首次建立了孕激素(P4)与 TPC 之间相互作用以及 TPC 的药物释放特性的基本认识。通过精心设计的溶剂浸渍技术制备的载有 P4 的 TPC 基 LADDD 能够以类似于基于 EVA 和硅酮的市售制剂的药理学相关速率释放 P4。此外,TPC 还表现出对广泛的植入物尺寸和复杂几何形状的出色 3D 可打印性。

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