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载有吖啶黄素的 3D 打印植入物治疗脑胶质母细胞瘤。

3D-printed implants loaded with acriflavine for glioblastoma treatment.

机构信息

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain.

出版信息

Int J Pharm. 2024 Nov 15;665:124710. doi: 10.1016/j.ijpharm.2024.124710. Epub 2024 Sep 12.

Abstract

Drug delivery routes play an essential role in determining the efficacy and safety of medications. This study focused on the development and optimization of 3D-printed reservoir type implants as a combinational therapy drug delivery system for Glioblastoma Multiforme (GBM) post-surgery, possessing also antibacterial properties. In this study, we used a multimodal agent, Acriflavine (ACF) as an alternative drug to treat GBM. To date, ACF is used only as an antiseptic agent, although it has been shown to possess strong anticancer activities. ACF and a low molecular weight PCL were loaded into 3D-printed reservoir-type implants for sustained drug delivery. The study demonstrated that ACF implants exhibited sustained drug release kinetics, with faster release during the initial 30 days, followed by a gradual decrease over 90 days. This controlled release profile enhances the effectiveness of ACF delivery to tumour targets while minimizing side effects associated with systemic administration. In vitro experiments confirmed the inhibitory activity of ACF against GBM cells compared to non-tumour cells. The study also highlighted the bacteriostatic effects of ACF, making the implants potentially useful for post-surgery infection management, particularly against S. aureus, a common bacterial infection associated with brain surgery. The long-term drug-release capabilities of the implants make them attractive candidates for both tumour inhibition and antibacterial treatment. The study suggests that the developed ACF delivery systems have the potential for future clinical studies. Their ability to provide increased drug efficacy without systemic toxicity makes them promising candidates for cancer therapy and post-surgery infection management.

摘要

药物输送途径在确定药物的疗效和安全性方面起着至关重要的作用。本研究专注于开发和优化 3D 打印储库型植入物作为多形性胶质母细胞瘤(GBM)手术后联合治疗药物输送系统,同时具有抗菌性能。在本研究中,我们使用多模态试剂吖啶黄素(ACF)作为替代药物来治疗 GBM。迄今为止,ACF 仅被用作防腐剂,尽管已经证明它具有很强的抗癌活性。ACF 和低分子量的 PCL 被加载到 3D 打印的储库型植入物中以实现持续的药物输送。研究表明,ACF 植入物表现出持续的药物释放动力学,在前 30 天内释放速度较快,随后在 90 天内逐渐减少。这种控制释放特性增强了 ACF 输送到肿瘤靶标的效果,同时最大限度地减少了与全身给药相关的副作用。体外实验证实了 ACF 对 GBM 细胞的抑制活性与非肿瘤细胞相比。该研究还强调了 ACF 的抑菌作用,使植入物有可能用于手术后感染的管理,特别是针对金黄色葡萄球菌,这是一种与脑外科手术相关的常见细菌感染。植入物的长期药物释放能力使它们成为肿瘤抑制和抗菌治疗的有吸引力的候选物。该研究表明,开发的 ACF 输送系统具有未来进行临床研究的潜力。它们在不产生全身毒性的情况下提高药物疗效的能力使它们成为癌症治疗和手术后感染管理的有前途的候选物。

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