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光固化聚乙二醇作为喷墨 3D 药物输送系统的生物墨水用于疏水性药物。

Photocurable poly(ethylene glycol) as a bioink for the inkjet 3D pharming of hydrophobic drugs.

机构信息

Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, Room 5121, Engineering V, P.O. Box: 951600, Los Angeles, CA 90095, USA.

Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, Room 5121, Engineering V, P.O. Box: 951600, Los Angeles, CA 90095, USA; Division of Advanced Prosthodontics and the Weintraub Center for Reconstructive Biotechnology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Int J Pharm. 2018 Jul 30;546(1-2):145-153. doi: 10.1016/j.ijpharm.2018.04.056. Epub 2018 Apr 26.

Abstract

Binder jetting and material extrusion are the two most common additive manufacturing techniques used to create pharmaceutical tablets. However, their versatility is limited since the powder component is present throughout the dosage forms fabricated by binder jet 3D printing and material extrusion 3D printing requires high operating temperatures. Conversely, material jetting allows for compositional control at a voxel level and can dispense material at room temperature. Unfortunately, there are a limited number of materials that are both printable and biocompatible. Therefore, the aim of this study was to engineer photocurable bioinks that are suitable for hydrophobic active pharmaceutical ingredients and have rapid gelation times upon visible light exposure. The resulting bioinks were comprised of poly(ethylene glycol) diacrylate (250 Da) as the crosslinkable monomer, Eosin Y as the photoinitiator, and methoxide-poly(ethylene glycol)-amine as the coinitiator. Additionally, poly(ethylene glycol) (200 Da) was added as a plasticizer to modulate the drug release profiles, and Naproxen was used as the model drug due to its high hydrophobicity. Various bioink formulations were dispensed into the bottom half of blank preform tablets - made via direct compression - using a piezoelectric nozzle, photopolymerized, and capped with the top half of the preform tablet to complete the pharmaceutical dosage form. Results from the release studies showed that drug release can be modulated by both the percent of poly(ethylene glycol) diacrylate in the formulation and the light exposure time used to cure the bioinks. These bioinks have the potential to expand the library of materials available for creating pharmaceutical tablets via inkjet printing with personalized drug dosages.

摘要

粉末喷射和材料挤出是用于制造药物片剂的两种最常见的增材制造技术。然而,它们的通用性有限,因为粉末成分存在于通过粘合剂喷射 3D 打印制造的剂型中,而材料挤出 3D 打印需要高温操作。相反,材料喷射允许在体素水平上进行组成控制,并且可以在室温下分配材料。不幸的是,可用的既具有打印性又具有生物相容性的材料数量有限。因此,本研究的目的是设计适用于疏水性活性药物成分的光固化生物墨水,并且在可见光照射下具有快速的凝胶化时间。所得的生物墨水由聚乙二醇二丙烯酸酯(250Da)作为可交联单体、曙红 Y 作为光引发剂和甲氧基聚乙二醇-胺作为共引发剂组成。此外,添加聚乙二醇(200Da)作为增塑剂来调节药物释放曲线,并且使用萘普生作为模型药物,因为其疏水性高。各种生物墨水制剂通过使用压电喷嘴分配到空白预制片剂的下半部分(通过直接压缩制成),然后用光聚合,并用预制片剂的上半部分覆盖以完成药物剂型。释放研究的结果表明,药物释放可以通过配方中聚乙二醇二丙烯酸酯的百分比和用于固化生物墨水的光暴露时间来调节。这些生物墨水有可能通过喷墨打印用个性化药物剂量来扩展可用于制造药物片剂的材料库。

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