In this study, a pH-responsive hydrogel consisting of a 4-arm poly(ethylene glycol)-block-poly(L-glutamic acid) (4a-PEG-PLG) copolymer was developed and used for the controlled release of peptide and protein drugs. It was found that the mechanical properties and degradation processes of the hydrogels could be tuned by changing the polymer concentrations. In vitro drug release results revealed that the release of insulin (or BSA) from hydrogel was highly dependent on the pH, i.e., less than 20% of insulin (or BSA) was released in the artificial gastric fluid (AGF) at 72 h, while close to 100% of insulin (or BSA) was released in the artificial intestinal fluid (AIF). It was because that the deprotonation of carboxyl groups in PLG block caused the disassembly, and even disintegration of the hydrogel in AGF, thereby resulting in accelerated drug release. Circular dichroism spectra showed that the bioactivities of insulin and BSA released from hydrogels were obviously unchanged compared to those of native insulin and BSA, respectively. Mouse fibroblast L929 cells were cultured on the surface of hydrogels and the viabilities of cultured cells were above 90% after incubation for 24 h, indicating that the hydrogels had good cytocompatibilities. Moreover, in vivo degradation evaluation disclosed that the formed hydrogels will completely degrade after 8 days, and the H&E staining study demonstrated the excellent biocompatibility of the as-prepared hydrogels. Therefore, the biocompatible and biodegradable 4a-PEG-PLG hydrogel may serve as a promising platform for pH-responsive drug delivery.

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在这项研究中，pH响应水凝胶由4臂聚乙二醇嵌段组成开发了聚（L-谷氨酸）（4a-PEG-PLG）共聚物，并将其用于肽和蛋白质药物的控释。发现可以通过改变聚合物浓度来调节水凝胶的机械性能和降解过程。体外药物释放结果表明，水凝胶中胰岛素（或BSA）的释放高度依赖于pH，即在72 h时，不到20％的胰岛素（或BSA）在人造胃液（AGF）中释放，而近100％的胰岛素（或BSA）则在人造肠液（AIF）中释放。这是因为PLG嵌段中羧基的去质子化导致AGF中水凝胶的分解，甚至分解，从而导致药物释放加速。圆二色性光谱表明，与天然胰岛素和BSA相比，从水凝胶中释放出的胰岛素和BSA的生物活性明显没有变化。将小鼠成纤维细胞L929细胞培养在水凝胶表面，孵育24小时后，细胞活力在90％以上，表明该水凝胶具有良好的细胞相容性。此外，体内降解评估表明，形成的水凝胶将在8天后完全降解，H＆E染色研究表明，所制备的水凝胶具有出色的生物相容性。因此，生物相容性和可生物降解的4a-PEG-PLG水凝胶可以作为pH响应药物传递的有前途的平台。小鼠成纤维细胞L929细胞在水凝胶表面培养，孵育24小时后细胞活力在90％以上，表明该水凝胶具有良好的细胞相容性。此外，体内降解评估表明，形成的水凝胶将在8天后完全降解，H＆E染色研究表明，所制备的水凝胶具有出色的生物相容性。因此，生物相容性和可生物降解的4a-PEG-PLG水凝胶可以作为pH响应药物传递的有前途的平台。将小鼠成纤维细胞L929细胞培养在水凝胶表面，孵育24小时后，细胞活力在90％以上，表明该水凝胶具有良好的细胞相容性。此外，体内降解评估表明，形成的水凝胶将在8天后完全降解，H＆E染色研究表明，所制备的水凝胶具有出色的生物相容性。因此，生物相容性和可生物降解的4a-PEG-PLG水凝胶可以作为pH响应药物传递的有前途的平台。体内降解评估表明，形成的水凝胶将在8天后完全降解，并且H＆E染色研究表明，所制备的水凝胶具有出色的生物相容性。因此，生物相容性和可生物降解的4a-PEG-PLG水凝胶可以作为pH响应药物传递的有前途的平台。体内降解评估表明，形成的水凝胶将在8天后完全降解，H＆E染色研究证明了所制备的水凝胶具有出色的生物相容性。因此，生物相容性和可生物降解的4a-PEG-PLG水凝胶可以作为pH响应药物传递的有前途的平台。

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