Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, 21321, Egypt.
Department of Chemistry, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia.
Sci Rep. 2024 Nov 25;14(1):29206. doi: 10.1038/s41598-024-80453-8.
This study involved synthesis of a novel antibacterial heterocyclic compound, sodium 2-(2-(3-phenyl-1, 2, 4-oxadiazol-5-yl) phenoxy) acetate abbreviated as Na-POPA. Further development of a biocompatible, pH-responsive hydrogel drug carrier prepared utilizing the natural polymers gelatin and sodium alginate. The compound loaded on the hydrogel represented new drug delivery system. Comprehensive characterization of Na-POPA was performed using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR), carbon-13 nuclear magnetic resonance (¹³C NMR), and high-resolution mass spectrometry (HRMS). The compound was loaded onto the sodium alginate/gelatin hydrogel carrier under feasible experimental conditions. The successful incorporation of Na-POPA into the hydrogel matrix was confirmed via scanning electron microscopy (SEM), powder X-ray diffraction (pXRD) analysis and FT-IR spectroscopy. Cytotoxicity assays revealed that the all the loaded and unloaded compound induced cell toxicity at large concentration much lower than many reported results. The hydrogel reduced the inherent cytotoxicity of Na-POPA and enhanced its biocompatibility. The release kinetics of Na-POPA from the hydrogel were evaluated spectrophotometrically at different pH conditions simulating biological fluids. The release rate at pH 1.2 was greater than the release at pH 6.8, with a higher cumulative release observed at pH 6.8. The release kinetics obeyed the pseudo-second-order kinetic model, indicating a controlled release mechanism influenced by the hydrogel's physicochemical properties. Electrochemical impedance spectroscopy and cyclic voltammetry further confirmed that the compound release was pH-dependent. The high swelling and solubility at pH 6.8 enhance the release. The larger amount released at 6.8 (target intestine) because of more solubility, leaching and swelling rather than shrinking.
本研究涉及一种新型抗菌杂环化合物的合成，即 2-(2-(3-苯基-1,2,4-恶二唑-5-基)苯氧基)乙酸钠，简称 Na-POPA。进一步开发了一种利用天然聚合物明胶和海藻酸钠制备的生物相容性、pH 响应水凝胶药物载体。负载在水凝胶上的化合物代表了新的药物传递系统。利用傅里叶变换红外光谱（FT-IR）、质子核磁共振（¹H NMR）、碳-13 核磁共振（¹³C NMR）和高分辨率质谱（HRMS）对 Na-POPA 进行了全面表征。在可行的实验条件下，将化合物负载到海藻酸钠/明胶水凝胶载体上。通过扫描电子显微镜（SEM）、粉末 X 射线衍射（pXRD）分析和 FT-IR 光谱证实了 Na-POPA 成功掺入水凝胶基质中。细胞毒性试验表明，所有负载和未负载的化合物在大浓度下诱导细胞毒性的能力都远低于许多报道的结果。水凝胶降低了 Na-POPA 的固有细胞毒性，提高了其生物相容性。通过在不同 pH 条件下（模拟生物流体）的分光光度法评估 Na-POPA 从水凝胶中的释放动力学。在 pH 1.2 时的释放速率大于在 pH 6.8 时的释放速率，在 pH 6.8 时观察到更高的累积释放。释放动力学符合伪二阶动力学模型，表明释放机制受到水凝胶物理化学性质的控制。电化学阻抗谱和循环伏安法进一步证实了化合物释放是 pH 依赖性的。在 pH 6.8 时的高溶胀和溶解度增强了释放。由于更多的溶解度、浸出和溶胀而不是收缩，在 6.8 时（目标肠道）释放的量更大。
