Acid and Glutathione Dual-Responsive, Injectable and Self-Healing Hydrogels for Controlled Drug Delivery
Acid and Glutathione Dual-Responsive, Injectable and Self-Healing Hydrogels for Controlled Drug Delivery
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DOI：
10.1021/acs.biomac.3c01274
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发表时间：
2024-02-20
影响因子：
6.2
通讯作者：
Yin，Jun
中科院分区：
文献类型：
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作者：
Zhu，Benshun;Zong，Tong;Yin，Jun
考虑到生理微环境的复杂性和手术感染的风险，仍然迫切需要开发一种具有多功能特性的水凝胶作为药物释放平台，包括良好的中性稳定性和敏感的多重刺激反应行为，以及可注射和自愈特性。在此，我们提出了一种易于制备的可注射的，具有酸和谷胱甘肽（GSH）双重反应性的自愈水凝胶，用于控制药物递送。最初，用二硫键对抗癌药物喜树碱（CPT）进行预修饰，并通过希夫碱反应与聚亚胺（PEI）结合，得到PEI-CPT。随后，IR780与胺基（IR780- nh2）和氧化海藻酸钠与醛基（OSA）通过Schiff碱反应合成OSA-IR780。通过将PEI-CPT水溶液与OSA-IR780简单混合，可在40 s内快速形成不同固含量的PEI-CPT/OSA-IR780水凝胶。这些水凝胶在中性条件下表现出显著的稳定性，并在暴露于以酸性条件和GSH浓度升高为特征的模拟肿瘤环境时控制CPT的释放。此外，由于动态亚胺交联网络，它们具有显著的可注射性和自愈性。此外，制备的水凝胶具有长期的生物降解性和生物相容性。总的来说，这些特征表明PEI-CPT/OSA-IR780水凝胶作为治疗递送载体的巨大潜力。
Considering the complexity of physiological microenvironments and the risks of surgical infection, there still remains critical demand to develop a hydrogel as a drug release platform with multifunctional properties, including good neutral stability and sensitive multiple stimuli-responsive behaviors, as well as injectable and self-healing properties. Herein, we present a facile preparation of injectable, self-healing hydrogels with acid and glutathione (GSH) dual-responsiveness for controlled drug delivery. Initially, the anticancer drug camptothecin (CPT) was premodified with disulfide bonds and attached to poly(ethylenimine) (PEI) via the Schiff base reaction, resulting in PEI-CPT. Subsequently, OSA-IR780 was synthesized through the Schiff base reaction involving IR780 with amine groups (IR780-NH2) and oxidized sodium alginate with aldehyde groups (OSA). The formation of PEI-CPT/OSA-IR780 hydrogels with various solid contents occurred rapidly within 40 s through a simple mixing process of the aqueous solution of PEI-CPT and OSA-IR780. These hydrogels exhibited remarkable stability under neutral conditions and controlled release of CPT upon exposure to simulated tumor environments characterized by acidic conditions and elevated GSH concentrations. Furthermore, they had significant injectable and self-healing properties due to the dynamically imine-cross-linked networks. In addition, the prepared hydrogels exhibited long-term biodegradability and biocompatibility. Collectively, these features indicate the great potential of PEI-CPT/OSA-IR780 hydrogels as therapeutic delivery vehicles.