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立体光固化成型(SLA)3D 打印膀胱内药物输送装置。

Stereolithography (SLA) 3D printing of a bladder device for intravesical drug delivery.

机构信息

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; FabRx Ltd., 3 Romney Road, Ashford, Kent TN24 0RW, UK; Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Facultad de Farmacia, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111773. doi: 10.1016/j.msec.2020.111773. Epub 2020 Dec 4.

Abstract

Intravesical instillation therapy is an alternative approach to oral medications for the treatment of severe bladder diseases, offering high drug concentrations at the site of action while minimising systemic side effects. However, therapeutic efficacy is often limited because of the short residence time of the drug in the bladder and the need for repeated instillations. This study reports, for the first time, the use of stereolithography (SLA) 3D printing to manufacture novel indwelling bladder devices using an elastic polymer to achieve extended and localised delivery of lidocaine hydrochloride. The devices were designed to be inserted into and retrieved from the bladder using a urethral catheter. Two types of bladder devices (hollow and solid) were prepared with a resilient material (Elastic Resin) incorporating three drug loads of lidocaine hydrochloride (10% w/w, 30% w/w and 50% w/w); a drug frequently used to treat interstitial cystitis and bladder pain. All of the devices showed acceptable blood compatibility, good resistance to compressive and stretching forces and were able to recover their original shape immediately once external forces were removed. In vitro drug release studies showed that a complete release of lidocaine was achieved within 4 days from the hollow devices, whereas the solid devices enabled sustained drug release for up to 14 days. SLA 3D printing therefore provides a new manufacturing route to produce bladder-retentive drug delivery devices using elastic polymers, and offers a revolutionary and personalised approach for clinical intravesical drug delivery.

摘要

膀胱内灌注治疗是治疗严重膀胱疾病的一种替代口服药物的方法,它在作用部位提供高浓度的药物,同时最大限度地减少全身副作用。然而,由于药物在膀胱中的停留时间短,需要反复灌注,治疗效果往往受到限制。本研究首次报道使用立体光刻(SLA)3D 打印技术制造新型留置膀胱装置,使用弹性聚合物实现盐酸利多卡因的延长和局部递送。这些装置设计为通过尿道导管插入和取出膀胱。使用弹性树脂(弹性树脂)制备了两种类型的膀胱装置(空心和实心),其中包含三种盐酸利多卡因的药物负载(10%w/w、30%w/w 和 50%w/w);盐酸利多卡因是一种常用于治疗间质性膀胱炎和膀胱疼痛的药物。所有装置均表现出良好的血液相容性、抗压和拉伸力的良好阻力,并且一旦去除外力,能够立即恢复其原始形状。体外药物释放研究表明,空心装置在 4 天内完全释放了盐酸利多卡因,而实心装置能够持续释放药物长达 14 天。因此,SLA 3D 打印为使用弹性聚合物生产膀胱留置药物输送装置提供了一种新的制造途径,并为临床膀胱内药物输送提供了一种革命性和个性化的方法。

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