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Carbon Dot Cross-Linked Gelatin Nanocomposite Hydrogel for pH-Sensing and pH-Responsive Drug Delivery
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-09-16 , DOI: 10.1021/acsbiomaterials.0c00982
Swarup Krishna Bhattacharyya 1 , Madhab Dule 2 , Raj Paul 3 , Jyotirmayee Dash 3 , Md Anas 3 , Tarun Kumar Mandal 3 , Poushali Das 1 , Narayan Chandra Das 1, 4 , Susanta Banerjee 1, 2
Affiliation  

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 in vitro 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.

中文翻译:

碳点交联明胶纳米复合水凝胶,用于pH敏感和pH敏感药物递送

绕过苛刻的胃酸性环境将治疗剂递送至肠区域一直是研究的重点。另一方面,在药物输送过程中监控系统的pH值是至关重要的诊断因素,因为许多治疗剂的活性和释放速率都取决于该系统。这项研究通过制造新型的纳米复合水凝胶用于肠道药物输送并同时接近中性pH值,从而回答了这两个问题。通过简单的溶剂浇铸方法可以制备出具有不同浓度碳点(CD)的明胶纳米复合材料(GNC)。在此,CD发挥双重作用,同时充当交联剂和生色团,从而减少了有毒交联剂的使用。提出的GNC水凝胶样品在接近中性的pH范围内可作为出色的pH传感器,可用于定量pH测量。模型抗菌药物(头孢曲氨酯)用于体外在胃pH(1.2)和肠pH(7.4)条件下进行药物释放研究。在24小时的研究中,与酸性介质相比,在pH 7.4下观察到了中等且持续的药物释放曲线。药物释放曲线表明,释放介质的pH和CD交联的百分比会影响药物释放速率。将释放数据与不同的经验方程式进行比较,以评估药物释放动力学,发现与Higuchi模型具有良好的一致性。通过肉汤微稀释法评估了头孢羟氨苄的抗菌活性,发现其保留并不受药物截留程序的阻碍。细胞活力测定表明,所有水凝胶样品,包括载药的GNC水凝胶,均具有可接受的细胞相容性和无毒性。
更新日期:2020-10-12
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