Prostate cancer is a leading cause of death in men and despite improved surgical procedures that aid tumor resection, the risk of recurrence after surgery as a result of positive resection margins remains significant. Adjuvant chemotherapy is often required but this is associated with toxicity. Improved ways of delivering highly toxic chemotherapeutic drugs in a more controlled and targeted manner after the prostate has been removed during surgery could reduce the risk of recurrence and avoid systemic toxicity. The aim of this study was to develop a novel drug-device combination tissue scaffold that can be used to deliver the chemotherapeutic agent, docetaxel, into the tissue cavity that is created following radical prostatectomy. The device component investigated consisted of highly porous, poly(dl-lactide-co-glycolide) microparticles made using thermally induced phase separation. A facile method was established for loading docetaxel with high efficiency within one hour. Sustained drug release was observed from the microparticles when placed into a dynamic system simulating tissue perfusion. The drug released from the microparticles into perfusates collected at regular time intervals inhibited colony formation and exhibited sustained cytotoxicity against 3D spheroids of PC3 prostate cancer cells over 10 days. In conclusion, this study demonstrates the concept of combining docetaxel with the biodegradable microparticles at the point of care is technically feasible for achieving an effective drug-device combination tissue scaffold. This approach could provide an effective new approach for delivering adjuvant chemotherapy following radical prostatectomy.

中文翻译：

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新型辅助根治性前列腺切除术的药物-药物组合组织支架。

前列腺癌是男性的主要死亡原因，尽管改善了有助于肿瘤切除的外科手术程序，但由于切除术阳性切缘导致的术后复发风险仍然很高。通常需要辅助化疗，但这与毒性有关。在手术切除前列腺后，以更可控和更有针对性的方式提供更高毒性的化学治疗药物的改进方法可以降低复发的风险并避免全身性毒性。这项研究的目的是开发一种新型的药物-装置组合组织支架，该支架可用于将化学治疗剂多西紫杉醇递送至根治性前列腺切除术后产生的组织腔内。所研究的设备组件由高度多孔的，使用热诱导相分离制得的聚（dl-丙交酯-共-乙交酯）微粒。建立了一种简便的方法，可在一小时内高效地加载多西他赛。当放置在模拟组织灌注的动态系统中时，从微粒中观察到了持续的药物释放。以规则的时间间隔从微粒释放到灌流液中的药物可抑制菌落形成，并在10天内对PC3前列腺癌细胞的3D球体表现出持续的细胞毒性。总之，这项研究证明了在护理时将多西紫杉醇与可生物降解的微粒结合的概念在技术上是可行的，以实现有效的药物-装置结合的组织支架。