酶交联法制备pH响应型聚(γ-谷氨酸)水凝胶,ACS Biomaterials Science & Engineering

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酶交联法制备pH响应型聚(γ-谷氨酸)水凝胶
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2022-02-01 , DOI: 10.1021/acsbiomaterials.1c01378
Meng Wei ₁ , Tomonori Inoue ₂ , Yu-I Hsu ₁ , Moon-Hee Sung ₃ , Tokuma Fukuoka _{2,

4} , Shiro Kobayashi ₂ , Hiroshi Uyama ₁

Affiliation

pH响应性水凝胶对于口服药物释放应用很重要，并且越来越需要它们来减少药物释放的不良副作用并改善药物吸收。本研究在辣根过氧化物酶（HRP）和过氧化氢（H ₂ O ₂ )。_{通过改变 HRP 和 H 2} O ₂的浓度来调节所得水凝胶的凝胶化速率、刚度、溶胀行为和孔径或 PGA-Tyr 的取代度 (DS)。水凝胶的pH响应性通过在不同pH值溶液中的溶胀率来评价，它们的pH响应性在pH 2.0和7.0溶液中表现出良好的可逆性。水凝胶在模拟肠液（SIF）中的降解速度快于模拟胃液（SGF）。此外，通过快速原位凝胶化将疏水性药物模型吲哚美辛（IM）封装在水凝胶中，并在 SGF 和 SIF 中实现了负载 IM 的水凝胶的 pH 依赖性药物释放。重要的是，当 IM 包埋在 pluronic F-127 中形成药物胶束时，具有高 DS 的 PGA-Tyr 负载 IM 胶束的水凝胶的突释在 SGF 中显着降低，并且在 SIF 中呈现持续的药物释放。因此，

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Preparation of pH-Responsive Poly(γ-glutamic acid) Hydrogels by Enzymatic Cross-Linking

pH-responsive hydrogels are important for oral drug release applications, and they are increasingly demanded to reduce the adverse side effects of drug release and improve drug absorption. In this study, a new type of pH-responsive hydrogel comprised of poly(γ-glutamic acid) modified with tyramine (PGA-Tyr) was developed through enzymatic cross-linking in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂). The gelation rate, stiffness, swelling behavior, and pore size of the resulting hydrogels were tuned by changing the concentrations of HRP and H₂O₂ or the degree of substitution (DS) of PGA-Tyr. The pH responsiveness of the hydrogels was evaluated by the swelling ratio in solutions with various pH values, and their pH responsiveness exhibited a good reversibility in pH 2.0 and 7.0 solutions. The degradation rate of the hydrogels in simulated intestinal fluid (SIF) was faster than that in simulated gastric fluid (SGF). Moreover, indomethacin (IM), a hydrophobic drug model, was encapsulated in the hydrogels by rapid in situ gelation, and the pH-dependent drug release of IM-loaded hydrogels was achieved in SGF and SIF. Importantly, when IM was entrapped in pluronic F-127 to form drug micelles, the burst release of the IM-micelle-loaded hydrogels with a high DS of PGA-Tyr was remarkably decreased in SGF, and sustained drug release was presented in SIF. Thus, pH-responsive PGA-based hydrogels have tremendous promise for biomedical applications, especially oral drug delivery.

更新日期：2022-02-01

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