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采用热熔挤出技术制备的三硫仑 3D 打印薄膜作为一种潜在的抗宫颈癌候选药物。

Disulfiram 3D printed film produced via hot-melt extrusion techniques as a potential anticervical cancer candidate.

机构信息

Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy Taibah University, Al Madinah AlMunawarah 30001, Saudi Arabia.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

Int J Pharm. 2023 Mar 25;635:122709. doi: 10.1016/j.ijpharm.2023.122709. Epub 2023 Feb 17.

Abstract

Cervical cancer is known globally as one of the most common health problems in women. Indeed, one of the most convenient approaches for its treatment is an appropriate bioadhesive vaginal film. This approach provides a local treatment modality, which inevitably decreases dosing frequency and improves patient compliance. Recently, disulfiram (DSF) has been investigated and demonstrated to possess anticervical cancer activity; therefore, it is employed in this work. The current study aimed to produce a novel, personalized three-dimensional (3D) printed DSF extended-release film using the hot-melt extrusion (HME) and 3D printing technologies. The optimization of the formulation composition and the HME and 3D printing processing temperatures was an important factor for overcoming the DSF heat-sensitivity issue. In addition, the 3D printing speed was specifically the most crucial parameter for alleviating heat-sensitivity concerns, which led to the production of films (F1 and F2) with an acceptable DSF content and good mechanical properties. The bioadhesion film study using sheep cervical tissue indicated a reasonable adhesive peak force (N) of 0.24 ± 0.08 for F1 and 0.40 ± 0.09 for F2, while the work of adhesion (N.mm) for F1 and F2 was 0.28 ± 0.14 and 0.54 ± 0.14, respectively. Moreover, the cumulative in vitro release data indicated that the printed films released DSF for up to 24 h. HME-coupled 3D printing successfully produced a patient-centric and personalized DSF extended-release vaginal film with a reduced dose and longer dosing interval.

摘要

宫颈癌是全球范围内女性最常见的健康问题之一。事实上,治疗宫颈癌最方便的方法之一是使用合适的生物粘附阴道膜。这种方法提供了局部治疗方式,不可避免地减少了用药频率,提高了患者的依从性。最近,研究发现双硫仑(DSF)具有抗宫颈癌活性,因此在本工作中使用了它。本研究旨在使用热熔挤出(HME)和 3D 打印技术生产一种新型的、个性化的 3D 打印 DSF 缓释膜。制剂组成和 HME 及 3D 打印加工温度的优化是克服 DSF 热敏性问题的重要因素。此外,3D 打印速度是缓解热敏性问题的关键参数,可生产出具有可接受 DSF 含量和良好机械性能的薄膜(F1 和 F2)。使用绵羊宫颈组织进行的生物粘附膜研究表明,F1 的合理粘附峰值力(N)为 0.24 ± 0.08,F2 的为 0.40 ± 0.09,而 F1 和 F2 的粘附功(N.mm)分别为 0.28 ± 0.14 和 0.54 ± 0.14。此外,体外累积释放数据表明,打印薄膜可在 24 小时内释放 DSF。HME 与 3D 打印相结合,成功地生产出了一种以患者为中心的、个性化的 DSF 缓释阴道膜,减少了剂量,延长了给药间隔。

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