Abstract：
Hydrogels hold significant promise as drug delivery systems due to their distinct advantage of sustained localized drug release. However, the challenge of regulating the initial burst release while achieving precise control over degradation and drug-release kinetics persists. Herein, we present an ABA-type triblock copolymer-based hydrogel system with precisely programmable degradation and release kinetics. The resulting hydrogels were designed with a hydrophilic poly(ethylene oxide) midblock and a hydrophobic end-block composed of polyethers with varying ratios of ethoxyethyl glycidyl ether and tetrahydropyranyl glycidyl ether acetal pendant possessing different hydrolysis kinetics. This unique side-chain strategy enabled us to achieve a broad spectrum of precise degradation and drug-release profiles under mildly acidic conditions while maintaining the cross-linking density and viscoelastic modulus, which is unlike the conventional polyester-based backbone degradation system. Furthermore, programmable degradation of the hydrogels and release of active therapeutic agent paclitaxel loaded therein are demonstrated in an in vivo mouse model by suppressing tumor recurrence following surgical resection. Tuning of the fraction of two acetal pendants in the end-block provided delicate tailoring of hydrogel degradation and the drug release capability to achieve the desired therapeutic efficacy. This study not only affords a facile means to design hydrogels with precisely programmable degradation and release profiles but also highlights the critical importance of aligning the drug release profile with the target disease.
摘要：
水凝胶由于其持续局部药物释放的独特优势而具有作为药物递送系统的显著希望。然而,调节初始突释，同时实现对降解和药物释放动力学的精确控制的挑战仍然存在。在这里，我们提出了一种基于ABA型三嵌段共聚物的水凝胶系统，具有精确的可编程降解和释放动力学。所得到的水凝胶被设计成具有亲水性聚(环氧乙烷)中间嵌段和疏水性末端嵌段,所述疏水性末端嵌段由具有不同水解动力学的不同比率的乙氧基乙基缩水甘油醚和四氢吡喃基缩水甘油醚缩醛侧基的聚醚组成。这种独特的侧链策略使我们能够在弱酸性条件下实现广泛的精确降解和药物释放曲线，同时保持交联密度和粘弹性模量，这与传统的聚酯基主链降解体系不同。此外，通过抑制手术切除后的肿瘤复发,在体内小鼠模型中证明了水凝胶的可编程降解和其中负载的活性治疗剂紫杉醇的释放。调节端块中的两个缩醛侧支的部分提供了水凝胶降解和药物释放能力的精细定制,以实现期望的治疗功效。这项研究不仅提供了一种简单的方法来设计具有精确可编程的降解和释放曲线的水凝胶，而且还强调了使药物释放曲线与目标疾病对齐的至关重要性。
