Myung Noehyun, Kang Hyun-Wook
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulju-gun 44919, South Korea.
Asian J Pharm Sci. 2024 Feb;19(1):100884. doi: 10.1016/j.ajps.2024.100884. Epub 2024 Jan 12.
Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer (TNBC), a highly aggressive disease with a poor prognosis. This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals, allowing for promising clinical outcomes with intensive treatment. However, the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance, limiting therapeutic efficacy and clinical benefit. Here, we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with time-programmed pulsatile release profiles. The implantable device can control the time between drug releases based on its internal microstructure design, which can be used to control dose density. The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar. Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects and . Under the same dose density conditions, device-based chemotherapy shows a higher anti-cancer effect and less toxic response than intratumoral injection. We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose, number of releases, and treatment duration of the dose-dense AC (doxorubicin and cyclophosphamide) regimen preferred for TNBC treatment. Dose density modulation inhibits tumor growth, metastasis, and the expression of drug resistance-related proteins, including p-glycoprotein and breast cancer resistance protein. To the best of our knowledge, local dose-dense chemotherapy has not been reported, and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.
剂量密集化疗是三阴性乳腺癌（TNBC）的首选一线治疗方法，TNBC是一种侵袭性很强且预后较差的疾病。这种治疗方法使用与传统化疗相同的药物剂量，但给药间隔更短，强化治疗可带来良好的临床效果。然而，这种治疗方法频繁的全身给药会导致全身毒性和患者依从性低，限制了治疗效果和临床获益。在此，我们报告通过植入具有时间编程脉冲释放曲线的3D打印装置来进行局部剂量密集化疗以治疗TNBC。该可植入装置可根据其内部微观结构设计控制药物释放之间的时间，从而可用于控制剂量密度。该装置由可生物降解材料制成，方便临床使用，并设计用于通过套管针进行微创植入。使用可编程释放的局部化疗的剂量密度变化可增强抗癌效果。在相同剂量密度条件下，基于装置的化疗比瘤内注射显示出更高的抗癌效果和更低的毒性反应。我们展示了利用可植入装置进行的局部化疗，该装置模拟了TNBC治疗首选的剂量密集AC（阿霉素和环磷酰胺）方案的药物剂量、释放次数和治疗持续时间。剂量密度调节可抑制肿瘤生长、转移以及耐药相关蛋白（包括P-糖蛋白和乳腺癌耐药蛋白）的表达。据我们所知，局部剂量密集化疗尚未见报道，我们的策略有望作为传统疗法的一种新替代方法，并提高抗癌效率。
