Sabbagh Hazem Abdul Kader, Hussein-Al-Ali Samer Hasan, Hussein Mohd Zobir, Abudayeh Zead, Ayoub Rami, Abudoleh Suha Mujahed
Department of Basic Pharmaceutical Science, Faculty of Pharmacy, Isra University, Amman 11622, Jordan.
Department of Chemistry, Faculty of Science, Isra University, Amman 11622, Jordan.
Polymers (Basel). 2020 Apr 1;12(4):772. doi: 10.3390/polym12040772.
The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (2 × 3 × 2) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl concentrations, whereas zeta potential depends only on the Alg and CaCl concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (-9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model ( between 0.956-0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.
本研究的目的是使用(2×3×2)×3 = 36全因子设计(FFD)开发并统计优化甲硝唑(MET)、壳聚糖(CS)和海藻酸盐(Alg)纳米颗粒(NP)纳米复合材料(MET-CS-AlgNPs)，以研究壳聚糖和海藻酸盐聚合物浓度以及氯化钙(CaCl)浓度对药物负载效率(LE)、粒径和zeta电位的影响。将CS、Alg和CaCl的浓度作为自变量，而药物负载量、粒径和zeta电位作为因变量。研究表明，负载效率和粒径取决于CS、Alg和CaCl的浓度，而zeta电位仅取决于Alg和CaCl的浓度。通过X射线衍射(XRD)、傅里叶变换红外光谱(FTIR)、热重分析(TGA)、扫描电子显微镜(SEM)和体外药物释放研究对MET-CS-AlgNPs纳米复合材料进行了表征。XRD数据表明，形成纳米复合材料时，MET的结晶特性转变为类无定形模式。MET-CS-AlgNPs的XRD图谱在2θ = 14.2°和22.1°处出现反射，表明在最佳条件下制备的纳米复合材料的平均直径为(165±20)nm，MET负载量为(46.0±2.1)%，zeta电位为(-9.2±0.5)mV。MET-CS-AlgNPs的FTIR数据显示了MET的一些谱带，如3283、1585和1413 cm，证实了MET-CS-AlgNPs纳米复合材料中药物的存在。MET-CS-AlgNPs优化样品的TGA显示失重70.2%，而CS-AlgNPs为55.3%，差异是由于在CS-AlgNPs中加入MET以形成MET-CS-AlgNPs纳米复合材料。MET从纳米复合材料中的释放显示出缓释特性，表明MET与聚合物之间存在相互作用。纳米复合材料表面光滑，呈球形。发现MET从其MET-CS-AlgNPs纳米复合材料中的释放曲线受二级动力学模型控制(在0.956 - 0.990之间)，在前50小时内释放超过90%，这表明通过纳米复合材料制剂可以延长MET药物的释放时间。
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