Bashir Shahid, Teo Yin Yin, Naeem Sumaira, Ramesh S, Ramesh K
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Centre of Ionics University of Malaya, Department of Physics, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
PLoS One. 2017 Jul 5;12(7):e0179250. doi: 10.1371/journal.pone.0179250. eCollection 2017.
There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers.
在过去几十年中，聚合物水凝胶的生物医学应用取得了重大进展。特别是，刺激响应性水凝胶已被视为一种精巧的药物递送系统，能够在特定时间内将药物递送至适当的作用部位。本工作描述了通过席夫碱机制，以戊二醛作为交联剂合成N-琥珀酰壳聚糖（NSC）的pH响应性半互穿网络（半IPN）水凝胶，并将聚（丙烯酰胺-共-丙烯酸）（聚（AAm-co-AA））嵌入N-琥珀酰壳聚糖网络中。通过傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、热重分析（TGA）和场发射扫描电子显微镜（FESEM）对物理化学相互作用进行了表征。合成的水凝胶具有多孔结构。在37°C下，在pH 7.4和pH 1.2的生理介质中分析了其溶胀能力。研究了不同量的NSC/聚（AAm-co-AA）和交联剂在pH 7.4和pH 1.2下制剂的溶胀性能。水凝胶在pH 7.4时显示出较高的溶胀率，而在pH 1.2时较低。还测定了溶胀动力学和扩散参数。观察了合成水凝胶对5-氟尿嘧啶（5-FU）的载药量、包封率和体外释放情况。体外释放曲线显示pH、NSC量、聚（AAm-co-AA）和交联剂对5-FU释放有显著影响。因此，在pH 7.4时观察到的药物释放比在pH 1.2时更快、更多。发现SP2对5-FU的最大包封率和释放率分别为72.45%和85.99%。药物释放动力学表明5-FU的控释机制符合非菲克ian趋势。从上述结果可以得出结论，合成的水凝胶有能力适应其作为靶向口服药物递送载体的潜在开发。
