微针贴片实现双药物释放，用于脑肿瘤的药物递送

原发性脑肿瘤多采用手术切除，但在某些情况下，因可能造成永久性损伤，肿瘤的薄层部分可能未被切除，残留肿瘤增加复发风险。本研究提出在手术后植入具有双重释放机制的微针贴片，用于多柔比星的给药。该贴片能直接向残留肿瘤递药，并在手术后立即启动化疗。通过有限元法进行了脑残留肿瘤药物递送的三维模拟，研究了四个关键参数的影响，包括药物突释比例、微针密度、微针长度和肿瘤微血管密度。结果显示，降低突释比例可减少最大平均浓度，但延长持续释放时间可提高药物的生物利用度。不同释放速率的AUC（曲线下面积）保持一致，因每次递药剂量相同。增加微针密度能在肿瘤大范围内积累药物，促进癌细胞死亡。较长微针能深入肿瘤层，提供更佳的治疗效果。肿瘤微血管密度的升高影响药物血管排出，降低疗效。该方案为构建局部药物递送系统提供了计算框架，旨在解决残留脑肿瘤的治疗难题。

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.