The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%-80% of their loads in 1-4 days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48 h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

中文翻译：

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聚酰胺胺树枝状聚合物介导的水凝胶，用于增强溶解度和抗癌药物递送。

水凝胶在抗癌药物输送中的应用引起了医学领域的极大兴趣。目前的癌症治疗方法，例如化疗和放射治疗，常常会引起严重的副作用，给患者带来严重的痛苦和严重的健康并发症。水凝胶是一种有吸引力的解决方案，因为它们可以精确地注射到体内的特定部位，促进封装药物的可持续释放。这种局部治疗方法在降低毒性水平和提高药物输送功效方面具有巨大潜力。在这项研究中，我们开发了一种含有聚酰胺胺（PAMAM）树枝状聚合物和聚乙二醇（PEG）的水凝胶递送系统，用于增强疏水性抗癌药物的溶解度和持续递送。所选的三种模型药物，例如水飞蓟宾、喜树碱和甲氨蝶呤，其水溶性有限，因此应用受到限制。在浓度为 45 mg/mL 的乙烯基砜官能化 PAMAM 树枝状聚合物存在下，水飞蓟宾、喜树碱和甲氨蝶呤的药物溶解度分别增加了 37 倍、4 倍和 10 倍。通过进一步交联功能化的 PAMAM 树枝状聚合物和硫醇化 PEG，我们成功开发了一种快速交联水凝胶，能够封装大量有效负载的可溶性癌症药物以实现持续释放。在水中，药物封装的水凝胶在 1-4 天内释放其负载的 30%-80%。对 J82 和 MCF7 细胞与不同剂量的药物封装水凝胶进行的 MTT 测定表明，48 小时后，所有三种药物在 J82 和 MCF7 细胞系上均观察到细胞毒性。值得注意的是，喜树碱对两种细胞系都表现出比水飞蓟宾和甲氨蝶呤更高的细胞毒性，尽管其溶解度较低，但在实验条件下可实现高达 95% 的细胞死亡。我们的实验提供的证据表明，PAMAM 树枝状聚合物介导的水凝胶系统显着提高了疏水性药物的溶解度并促进其持续释放。这些发现使该系统成为用于肿瘤内癌症治疗的疏水性药物的受控递送的有前景的平台。