Khodayar Shokouh, Shushizadeh Mohammad Reza, Tahanpesar Elham, Makhmalzadeh Behzad Sharif, Sanaeishoar Haleh
Department of Chemistry, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran.
Marine Pharmaceutical Science Research Center and Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz Iran.
Curr Org Synth. 2023 Nov 3. doi: 10.2174/0115701794210967231016055949.
The aims of this study are to synthesize new derivatives of sodium alginate that improve the inherent properties, such as hydrogel strengthening, and create environmental sensitivity, such as pH sensitivity, for use in drug delivery.
Today, hydrogels, due to outstanding properties such as biodegradability, biocompatibility, mechanical properties, and response to stimuli properties, are widely used as harmless biomaterials in various fields in drug delivery, wound dressing, and tissue engineering. Stimulus-sensitive polymers significantly respond to slight changes in their environment. Different types of stimuli are used to influence the properties of polymers, the most important of which are temperature and pH because these are two vital factors in the human body; hence, temperature-sensitive and pHsensitive hydrogels have been extensively studied. The ability to absorb water and swell the hydrogel is due to hydrophilic chains in the hydrogel network, and water absorption by hydrogel can be controlled by response to the stimuli. Since hydrogels mimic human tissue, the ability to retain water in them is essential. As a result, it is considered in many biomedical drug delivery systems. Stimulusresponsive swelling can control diffusion out of and into the hydrogel network, which allows temporal and spatial control of drug release. When a drug is loaded onto a biodegradable and stimulisensitive hydrogel, the drug delivery system has the added advantage of sustained release of the drug, which reduces side effects.
In this study, two different hydrocarbons, [1,3-diaminopropane (DAP)] as a short-chain hydrocarbon, and [1,7-diaminoheptane (DAH)] as a long-chain hydrocarbon were grafted onto three types ofsodium alginate (SA), through amide bond linkages. The hydrogel copolymer matrices were compared with sodium alginate (SA) beads. The graft copolymers were characterized using FTIR, 1HNMR, XRD spectroscopy, elemental analysis (CHNS) and thermal analysis (TGA, DTA and DSC). An environmental scanning electron microscope (ESEM) was used to investigate the surface morphology of hydrogels.
Effects of variables such as the length of hydrocarbon chains cross-linked to alginate, temperature, pH, and cross-linkers on the properties of hydrogels investigated in the temperature range of 2-70 ˚C and two different pH values (4.4 and 7.4). The results showed that when the hydrocarbon chain length of diamines decreases, the extent of cross-linking and strength of the hydrogels are increased. Other results suggest that the hydrogels obtained from high-viscosity alginate derivatives had positive pH sensitivity. Hydrogels prepared in this study demonstrated good mechanical and swelling ratios that are necessary for wound dressing.
DAP-g-SA and DAH-g-SA pH-sensitive hydrogels were successfully synthesized through amide bond linkages. The new synthesis derivatives showed lower swelling levels at low pH (4.4). In contrast, their swelling levels at higher pH (7.4) were significantly enhanced. Higher swelling degree could be obtained at high pH. pH-responsive hydrogels are especially useful for various biological applications due to their unique feature of controlled swelling, biodegradability, biocompatibility, and fluid retention in their network structures. pH-responsive hydrogels, as intelligent systems, can be used in controlled-release drug delivery systems such as insulin delivery.
本研究的目的是合成海藻酸钠的新衍生物，以改善其固有特性，如增强水凝胶性能，并赋予其环境敏感性，如pH敏感性，用于药物递送。
如今，水凝胶因其具有生物可降解性、生物相容性、机械性能和对刺激的响应特性等优异性能，在药物递送、伤口敷料和组织工程等各个领域被广泛用作无害生物材料。刺激敏感型聚合物对其环境的微小变化有显著响应。不同类型的刺激被用于影响聚合物的性能，其中最重要的是温度和pH，因为它们是人体中的两个重要因素；因此，温度敏感型和pH敏感型水凝胶已得到广泛研究。水凝胶吸收水分并膨胀的能力归因于水凝胶网络中的亲水链，并且水凝胶的吸水性可通过对刺激的响应来控制。由于水凝胶模拟人体组织，在其中保留水分的能力至关重要。因此，它在许多生物医学药物递送系统中得到考虑。刺激响应性肿胀可控制药物进出水凝胶网络的扩散，从而实现药物释放的时空控制。当药物负载到可生物降解且对刺激敏感的水凝胶上时，药物递送系统具有药物持续释放的额外优势，这可减少副作用。
在本研究中，两种不同的碳氢化合物，作为短链碳氢化合物的[1,3 - 二氨基丙烷（DAP）]和作为长链碳氢化合物的[1,7 - 二氨基庚烷（DAH）]，通过酰胺键连接嫁接到三种类型的海藻酸钠（SA）上。将水凝胶共聚物基质与海藻酸钠（SA）珠进行比较。使用傅里叶变换红外光谱（FTIR）、核磁共振氢谱（1HNMR）、X射线衍射光谱（XRD）、元素分析（CHNS）和热分析（TGA、DTA和DSC）对接枝共聚物进行表征。使用环境扫描电子显微镜（ESEM）研究水凝胶的表面形态。
在2 - 70˚C的温度范围和两个不同的pH值（4.4和7.4）下，研究了与藻酸盐交联的碳氢链长度、温度、pH和交联剂等变量对水凝胶性能的影响。结果表明，当二胺的碳氢链长度减小时，水凝胶的交联程度和强度增加。其他结果表明，由高粘度藻酸盐衍生物获得的水凝胶具有正pH敏感性。本研究制备的水凝胶表现出良好的机械性能和膨胀率，这是伤口敷料所必需的。
通过酰胺键连接成功合成了DAP - g - SA和DAH - g - SA pH敏感型水凝胶。新的合成衍生物在低pH（4.4）下显示出较低的膨胀水平。相比之下，它们在较高pH（7.4）下的膨胀水平显著增强。在高pH下可获得更高的膨胀度。pH响应型水凝胶由于其可控膨胀、生物可降解性、生物相容性以及在其网络结构中保留流体的独特特性，对于各种生物应用特别有用。pH响应型水凝胶作为智能系统，可用于控释药物递送系统，如胰岛素递送。
