本文介绍了一项针对靶向和局部输送癌症药物的实验和分析研究的结果。研究使用了聚乳酸-聚乙二醇酸-聚己内酯（PLGA-PCL）复合聚合物制备的靶向药物载体微球。在体外持续释放试验中，使用了装载有靶向药物（prodigiosin-EphA2或paclitaxel-EphA2）和对照药物（Prodigiosin (PGS)和paclitaxel (PTX)）的微球，通过详细的热力学驱动药物释放动力学，在三个月的时间范围内进行了研究。体外实验结果表明，药物具有持续而局部的释放，其释放过程符合非菲克扩散的Korsmeyer-Peppas动力学模型，适用于37℃（体温）、41℃和44℃（高温）的温度范围。通过体外的alamar blue实验和流式细胞术，研究了不同药物载体配方的细胞毒性和细胞死亡情况，发现在三阴性乳腺癌细胞（MDA-MB 231）中存在细胞抑制和迟发性凋亡。随后，对4周龄无胸腺的裸鼠进行了体内实验，通过皮下植入三阴性乳腺癌细胞（TNBC），结果显示EphA2结合药物的局部释放在局部手术切除后完全消除了残留肿瘤。最后，对安乐死的小鼠进行了外体组织病理学分析，结果显示治疗12周后肝、肾和肺中没有乳腺癌转移和细胞毒性。讨论了这些结果对于开发特定靶向、局部和持续释放药物的EphA2结合药物配方以消除局部复发的TNBC肿瘤的意义。© 2023. 作者。

The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer-Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection.© 2023. The Author(s).