School of Nano Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
Materials Science Centre, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
ACS Biomater Sci Eng. 2020 Oct 12;6(10):5662-5674. doi: 10.1021/acsbiomaterials.0c00982. Epub 2020 Sep 30.
Delivery of therapeutics to the intestinal region bypassing the harsh acidic environment of the stomach has long been a research focus. On the other hand, monitoring a system's pH during drug delivery is a crucial diagnosis factor as the activity and release rate of many therapeutics depend on it. This study answered both of these issues by fabricating a novel nanocomposite hydrogel for intestinal drug delivery and near-neutral pH sensing at the same time. Gelatin nanocomposites (GNCs) with varying concentrations of carbon dots (CDs) were fabricated through simple solvent casting methods. Here, CDs served a dual role and simultaneously acted as a cross-linker and chromophore, which reduced the usage of toxic cross-linkers. The proposed GNC hydrogel sample acted as an excellent pH sensor in the near-neutral pH range and could be useful for quantitative pH measurement. A model antibacterial drug (cefadroxil) was used for the drug release study at gastric pH (1.2) and intestinal pH (7.4) conditions. A moderate and sustained drug release profile was noticed at pH 7.4 in comparison to the acidic medium over a 24 h study. The drug release profile revealed that the pH of the release medium and the percentage of CDs cross-linking influenced the drug release rate. Release data were compared with different empirical equations for the evaluation of drug release kinetics and found good agreement with the Higuchi model. The antibacterial activity of cefadroxil was assessed by the broth microdilution method and found to be retained and not hindered by the drug entrapment procedure. The cell viability assay showed that all of the hydrogel samples, including the drug-loaded GNC hydrogel, offered acceptable cytocompatibility and nontoxicity. All of these observations illustrated that GNC hydrogel could act as an ideal pH-monitoring and oral drug delivery system in near-neutral pH at the same time.
将治疗剂递送到肠道区域以绕过胃的恶劣酸性环境一直是研究的重点。另一方面，在药物输送过程中监测系统的 pH 值是一个关键的诊断因素，因为许多治疗剂的活性和释放速率取决于它。本研究通过同时制造用于肠道药物输送和近中性 pH 感测的新型纳米复合水凝胶来同时解决这两个问题。通过简单的溶剂浇铸方法制造了具有不同浓度碳点 (CD) 的明胶纳米复合材料 (GNC)。在这里，CD 具有双重作用，同时充当交联剂和生色团，从而减少了有毒交联剂的使用。所提出的 GNC 水凝胶样品在近中性 pH 范围内表现出优异的 pH 传感器性能，可用于定量 pH 测量。使用模型抗菌药物（头孢羟氨苄）在胃 pH（1.2）和肠 pH（7.4）条件下进行药物释放研究。与酸性介质相比，在 24 小时研究中在 pH 7.4 下观察到温和且持续的药物释放曲线。药物释放曲线表明，释放介质的 pH 值和 CD 交联的百分比影响药物释放速率。释放数据与不同的经验方程进行比较，以评估药物释放动力学，并与 Higuchi 模型吻合良好。通过肉汤微量稀释法评估头孢羟氨苄的抗菌活性，发现药物包埋过程保留了其抗菌活性且未受到阻碍。细胞活力测定表明，包括载药 GNC 水凝胶在内的所有水凝胶样品均表现出可接受的细胞相容性和无毒性。所有这些观察结果表明，GNC 水凝胶可以同时作为理想的 pH 监测和口服药物递送系统，在近中性 pH 下发挥作用。
