Suhail Muhammad, Vu Quoc Lam, Wu Pao-Chu
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Department of Clinical Pharmacy, Thai Nguyen University of Medicine and Pharmacy, 284 Luong Ngoc Quyen Str., Thai Nguyen 24000, Vietnam.
Gels. 2022 Mar 26;8(4):207. doi: 10.3390/gels8040207.
In this study, novel pH-responsive polymeric β-cyclodextrin--poly(acrylic acid/itaconic acid) hydrogels were fabricated by the free radical polymerization technique. Various concentrations of β-cyclodextrin, acrylic acid, and itaconic acid were crosslinked by ethylene glycol dimethacrylate in the presence of ammonium persulfate. The crosslinked hydrogels were used for the controlled delivery of theophylline. Loading of theophylline was conducted by the absorption and diffusion method. The fabricated network of hydrogel was evaluated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). The crosslinking among hydrogel contents and drug loading by the fabricated hydrogel were confirmed by FTIR analysis, while TGA indicated a high thermal stability of the prepared hydrogel as compared to pure β-cyclodextrin and itaconic acid. The high thermal stability of the developed hydrogel indicated an increase in the thermal stability of β-cyclodextrin and itaconic acid after crosslinking. Similarly, a decrease in crystallinity of β-cyclodextrin and itaconic acid was observed after crosslinking, as evaluated by XRD analysis. SEM revealed an irregular and hard surface of the prepared hydrogel, which may be correlated with strong crosslinking among hydrogel contents. Crosslinked insoluble and uncrosslinked soluble fractions of hydrogel were evaluated by sol-gel analysis. An increase in gel fraction was seen with the increase in compositions of hydrogel contents, while a decrease in sol fraction was observed. Dynamic swelling and dissolution studies were performed in three various buffer solutions of pH 1.2, 4.6, and 7.4, respectively. Maximum swelling and drug release were observed at higher pH values as compared to the lower pH value due to the deprotonation and protonation of functional groups of the hydrogel contents; thus, the pH-sensitive nature of the fabricated hydrogel was demonstrated. Likewise, water penetration capability and polymer volume were evaluated by porosity and polymer volume studies. Increased incorporation of β-cyclodextrin, acrylic acid, and itaconic acid led to an increase in swelling, drug release, drug loading, and porosity of the fabricated hydrogel, whereas a decrease was detected with the increasing concentration of ethylene glycol dimethacrylate. Conclusively, the prepared hydrogel could be employed as a suitable and promising carrier for the controlled release of theophylline.
在本研究中，通过自由基聚合技术制备了新型pH响应性聚合物β-环糊精-聚（丙烯酸/衣康酸）水凝胶。在过硫酸铵存在下，各种浓度的β-环糊精、丙烯酸和衣康酸通过乙二醇二甲基丙烯酸酯交联。交联水凝胶用于茶碱的控释。茶碱的负载通过吸收和扩散法进行。通过傅里叶变换红外光谱（FTIR）、热重分析（TGA）、X射线衍射（XRD）和扫描电子显微镜（SEM）对制备的水凝胶网络进行了评估。FTIR分析证实了水凝胶成分之间的交联以及制备的水凝胶对药物的负载，而TGA表明与纯β-环糊精和衣康酸相比，制备的水凝胶具有高热稳定性。所制备水凝胶的高热稳定性表明交联后β-环糊精和衣康酸的热稳定性有所提高。同样，通过XRD分析评估，交联后β-环糊精和衣康酸的结晶度降低。SEM显示制备的水凝胶表面不规则且坚硬，这可能与水凝胶成分之间的强交联有关。通过溶胶-凝胶分析评估了水凝胶的交联不溶性和未交联可溶性部分。随着水凝胶成分组成的增加，凝胶分数增加，而溶胶分数降低。分别在pH值为1.2、4.6和7.4的三种不同缓冲溶液中进行了动态溶胀和溶解研究。由于水凝胶成分官能团的去质子化和质子化，与较低pH值相比，在较高pH值下观察到最大溶胀和药物释放；因此，证明了所制备水凝胶的pH敏感性。同样，通过孔隙率和聚合物体积研究评估了水渗透能力和聚合物体积。β-环糊精、丙烯酸和衣康酸掺入量的增加导致所制备水凝胶的溶胀、药物释放、药物负载和孔隙率增加，而随着乙二醇二甲基丙烯酸酯浓度的增加则检测到降低。总之，所制备的水凝胶可作为茶碱控释的合适且有前景的载体。
