原发性脑肿瘤主要通过手术切除程序进行治疗。然而，在某些情况下，由于可能造成永久性损伤，一薄层肿瘤可能会保留在切除过程之外；这些残留的肿瘤使患者面临肿瘤复发的风险。这项研究介绍了使用手术后植入的微针贴片和双释放机制来施用阿霉素。所提出的贴片能够直接向残留肿瘤给药并在手术后立即开始化疗。基于有限元方法对大脑残留肿瘤的药物输送进行了三维模拟。研究了四个重要参数对药物递送的影响，包括爆发相释放的药物分数、贴片上微针的密度、微针的长度和肿瘤的微血管密度。模拟结果表明，降低初始爆发阶段释放的药物分数会降低最大平均浓度，但持续较长时间的持续释放会增加游离药物的生物利用度。然而，由于每种情况下提供的药物剂量相同，不同释放速率的曲线下面积 (AUC) 保持不变。通过增加贴片上微针的密度，可以在肿瘤的广泛区域提供浓度积累，从而诱导更多的癌细胞死亡。对不同长度的比较分析表明，较长的微针有利于深入穿透肿瘤层，并且由于暴露于化疗药物的肿瘤区域较大，因此呈现出更好的治疗反应。此外，作为肿瘤微环境的特征，高微血管密度对药物的微血管引流具有显着影响，从而降低治疗反应结果。我们的方法提供了一个计算框架，用于创建局部药物输送系统并解决与残留脑肿瘤相关的挑战。© 2024。控释协会。

Primary brain tumors are mostly managed using surgical resection procedures. Nevertheless, in certain cases, a thin layer of tumors may remain outside of the resection process due to the possibility of permanent injury; these residual tumors expose patients to the risk of tumor recurrence. This study has introduced the use of microneedle patches implanted after surgery with a dual-release mechanism for the administration of doxorubicin. The proposed patches possess the capability to administer drugs directly to the residual tumors and initiate chemotherapy immediately following surgical procedures. Three-dimensional simulation of drug delivery to residual tumors in the brain has been performed based on a finite element method. The impact of four important parameters on drug delivery has been investigated, involving the fraction of drug released in the burst phase, the density of microneedles on the patch, the length of microneedles, and the microvascular density of the tumor. The simulation findings indicate that lowering the fraction of drug released in the initial burst phase reduces the maximum average concentration, but the sustained release that continues for a longer period, increasing the bioavailability of free drug. However, the area under curve (AUC) for different release rates remains unchanged due to the fact that an identical dose of drug is supplied in each instance. By increasing the density of microneedles on the patch, concentration accumulation is provided over an extensive region of tumor, which in turn induces more cancer cell death. A comparative analysis of various lengths reveals that longer microneedles facilitate profound penetration into the tumor layers and present better therapeutic response due to extensive area of the tumor which is exposure to chemotherapeutic drugs. Furthermore, high microvascular density, as a characteristic of the tumor microenvironment, is shown to have a significant impact on the blood microvessels drainage of drugs and consequently lower therapeutic response outcome. Our approach offers a computational framework for creating localized drug delivery systems and addressing the challenges related to residual brain tumors.© 2024. Controlled Release Society.