A pH-responsive, biocompatible, and non-toxic citric acid cross-linked polysaccharide-based hydrogel from Salvia spinosa L. offering zero-order drug release
A pH-responsive, biocompatible, and non-toxic citric acid cross-linked polysaccharide-based hydrogel from Salvia spinosa L. offering zero-order drug release
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DOI：
10.1016/j.jddst.2022.103144
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发表时间：
2022-02-08
影响因子：
5
通讯作者：
Sheikh, Fatima Akbar
中科院分区：
文献类型：
--
作者：
Ali, Arshad;Hussain, Muhammad Ajaz;Sheikh, Fatima Akbar
用1.25%、2.5%、5.0%和10.0%四种不同浓度的柠檬酸(CA)对刺丹参种子水凝胶进行化学交联。通过傅立叶变换红外光谱分析，证实了CA-CL-SSH的合成。CA-CL-SSH表现出与SSH相同的热稳定性。与pH 1.2、6.8和7.4的缓冲液相比，CA-CL-SSH在去离子水(DW)中表现出最大的溶胀，其顺序为pH 1.2<；pH 6.8<；pH 7.4<；DW。CA-CL-SSH(2.5%CA)在pH 7.4和1.2、DW和生理盐水以及DW和乙醇中的刺激响应溶胀和去胀(开-关开关)行为是可逆的。CA-CL-SSH对醋氯芬酸的释放遵循零级动力学和非Fickian扩散机制。体内放射学图像显示以CA-CL-SSH为基础的片剂在GIT中存在9h。血液相容性研究证实了CA-CL-SSH的非血栓形成和非溶血潜能。由于没有任何死亡和毒性影响，急性口服毒性研究显示了其安全性。因此，CA-CL-SSH是一种新型的刺激响应型、生物相容性好、无毒的多糖基生物材料，具有开发零级动力学缓释给药系统的潜力。
Salvia spinosa seeds hydrogel (SSH) was chemically cross-linked with four different concentrations of citric acid (CA), i.e., 1.25%, 2.5%, 5.0%, and 10.0%. The fabrication of CA cross-linked SSH (CA-cl-SSH) was confirmed through Fourier transform infrared spectroscopic analyses. The CA-cl-SSH appeared thermally as stable as SSH. The CA-cl-SSH was found pH-sensitive and exhibited maximum swelling in deionized water (DW) as compared to the buffers of pH 1.2, 6.8, and 7.4 following the order pH 1.2 < pH 6.8 < pH 7.4 < DW. Stimuli-responsive swelling and deswelling (on-off switching) behavior of CA-cl-SSH (2.5% CA) was found reversible at pH 7.4 and 1.2, in DW and normal saline, and DW and ethanol. CA-cl-SSH sustained the release of aceclofenac following the zero-order kinetics and non-Fickian diffusion mechanism. The in vivo radiographic images revealed the presence of CA-cl-SSH-based tablet formulation in GIT for 9 h. Hemocompatibility studies confirmed the nonthrombogenic and non-hemolytic potential of CA-cl-SSH. Acute oral toxicity study presented its safety profile owing to the absence of any mortality and toxic effects. Therefore, it can be concluded that CA-cl-SSH is a novel stimuli-responsive, biocompatible, and non-toxic polysaccharide-based biomaterial having the potential for the development of sustained-release drug delivery system following zero-order kinetics.