Conventional intravenous or oral administration of a combination of chemotherapeutics displays poor bioavailability and induces undesirable systemic toxicity. Therefore, localized delivery of such chemotherapeutic combinations using polymeric hydrogels is expected to help in enhancing drug efficacy and reducing systemic toxicity. In this manuscript, we have utilized a chitosan-catechol based hydrogel (CAT-Gel) assembled through catechol-Fe(III) coordinative interactions for localized combination therapy in murine lung and breast cancer models. CAT-Gel offers a unique blend of material properties such as injectability and self-healing along with useful biological attributes like their noncytotoxic and nonhemolytic nature. The amphipathic nature of this hydrogel enabled us to incorporate a recipe of hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic docetaxel (DTX) anticancer drugs. Rheology studies confirmed the self-healing nature of this chimeric hydrogel even after drug loading. CAT-Gel was retained for more than 40 days in mice upon subcutaneous injection. The sequential and sustained release of the entrapped DOX and DTX from the hydrogel resulted in synergistic therapeutic effect with increased median survival against murine lung and breast cancer models. Therefore, CAT-Gel provides a new coordinatively assembled biocompatible scaffold for localized delivery of chemotherapeutic drugs.

中文翻译：

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可注射的自修复嵌合儿茶酚-Fe（III）水凝胶用于局部联合癌症治疗

常规静脉内或口服联合化疗药物显示出较差的生物利用度，并引起不良的全身毒性。因此，预期使用聚合物水凝胶局部递送此类化学治疗组合物将有助于增强药物功效并降低全身毒性。在本手稿中，我们利用通过儿茶酚-铁（III）协同相互作用组装的壳聚糖-邻苯二酚基水凝胶（CAT-Gel）在鼠类肺癌和乳腺癌模型中进行了局部联合治疗。CAT-Gel提供了材料特性（如可注射性和自我修复）以及有用的生物学特性（如它们的非细胞毒性和非溶血性）的独特融合。这种水凝胶的两亲性质使我们能够纳入亲水性阿霉素盐酸盐（DOX）和疏水性多西紫杉醇（DTX）抗癌药的配方。流变学研究证实了这种嵌合水凝胶即使在加载药物后也具有自愈特性。皮下注射后，CAT-Gel在小鼠体内保留了40天以上。从水凝胶中连续捕集的DOX和DTX持续释放导致协同治疗效果，并提高了针对鼠类肺癌和乳腺癌模型的中位生存期。因此，CAT-Gel提供了一种新的协调组装的生物相容性支架，用于局部递送化疗药物。皮下注射后，CAT-Gel在小鼠体内保留了40天以上。从水凝胶中连续捕集的DOX和DTX持续释放导致协同治疗效果，并提高了针对鼠类肺癌和乳腺癌模型的中位生存期。因此，CAT-Gel提供了一种新的协调组装的生物相容性支架，用于局部递送化疗药物。皮下注射后，CAT-Gel在小鼠体内保留了40天以上。从水凝胶中连续捕集的DOX和DTX持续释放导致协同治疗效果，并提高了针对鼠类肺癌和乳腺癌模型的中位生存期。因此，CAT-Gel提供了一种新的协调组装的生物相容性支架，用于局部递送化疗药物。