Preparation of self-healing oxidized sodium alginate-carboxymethyl chitosan hydrogel for sustained drug release
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摘要: 本研究基于动态亚胺键合成了一种具有自修复性能的氧化海藻酸钠-羧甲基壳聚糖水凝胶(OSA-CMCS)。通过海藻酸钠的糖醛酸，合成了OSA，并通过与CMCS的席夫碱反应制备了具有不同交联度的自修复OSA-CMCS水凝胶，研究了OSA-CMCS水凝胶的微观形态、黏弹性能、溶胀性能、自修复性能、酶促降解性能和体外药物释放性能。结果表明，随着OSA与CMCS配比的增加，水凝胶的交联度逐渐增加，溶胀比逐渐减小。OSA-CMCS水凝胶具有高度孔隙化且孔隙之间相互连通的结构特点，孔径大小在20~100 μm范围内。室温条件下，OSA-CMCS水凝胶在无外界刺激时6 h能够实现自修复。OSA-CMCS水凝胶具有可降解性，并随着交联度的增大，降解速度减慢。OSA-CMCS水凝胶对水溶性药物吉西他滨具有缓释作用，药物释放时间可达4天。Abstract: The self-healing oxidized sodium alginate-carboxymethyl chitosan hydrogel (OSA-CMCS) was synthesized based on dynamic imine bonds. OSA was synthesized by oxidizing the uronic acid of sodium alginate, and self-healing OSA-CMCS hydrogels with different crosslinking degrees were prepared by Schiff base reaction with carboxymethyl chitosan, analyzed the microscopic morphology, viscoelastic properties, swelling properties, self-healing properties, enzymatic degradation properties and in vitro drug release properties of OSA-CMCS hydrogels. The results show that as the ratio of OSA to CMCS increase, the degree of crosslinking of the hydrogel gradually increase and the swelling ratio gradually decrease. OSA-CMCS hydrogel has the structural characteristics of highly porous and interconnected pores, and the pore size is in the range of 20-100 μm. At room temperature, OSA-CMCS hydrogel can realize self-healing within 6 hours without external stimulation. OSA-CMCS hydrogel is degradable, and as the degree of crosslinking increase, the degradation rate slow down. OSA-CMCS hydrogel has a slow-release effect on the water-soluble drug gemcitabine, and the drug release time can reach 4 days.
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Key words:
- self-healing /
- oxidized sodium alginate /
- carboxymethyl chitosan /
- hydrogel /
- sustained drug release
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图 1 氧化海藻酸钠-羧甲基壳聚糖(OSA-CMCS)水凝胶的合成路线
Figure 1. Synthetic route of oxidized sodium alginate-carboxymethyl chitosan (OSA-CMCS) hydrogels
图 2 SA和OSA的FTIR图谱 (a) 和核磁谱图 (b)
Figure 2. FTIR spectra (a) and 1H NMR spectra (b) of SA and OSA
图 3 OSA、CMCS和OSA-30wt%CMCS、OSA-40wt%CMCS，OSA-50wt%CMCS水凝胶的FTIR图谱
Figure 3. FTIR spectra of OSA, CMCS and OSA-30wt%CMCS, OSA-40wt%CMCS, OSA-50wt%CMCS hydrogels
图 4 OSA-30wt%CMCS (a)、OSA-40wt%CMCS (b) 和OSA-50wt%CMCS (c) 水凝胶的SEM图像
Figure 4. SEM images of surface morphology of lyophilized OSA-30wt%CMCS (a), OSA-40wt%CMCS (b) and OSA-50wt%CMCS (c) hydrogels
图 5 OSA-40wt%CMCS水凝胶的自修复过程((a)罗丹明B染色水凝胶；(b)原始和染色水凝胶相拼接；(c)拼接水凝胶放置2 h；(d)镊子夹起自修复水凝胶；(e)测量自修复水凝胶直径；(f)拉伸自修复水凝胶)
Figure 5. Photographs of self-healing process of the OSA-40wt%CMCS hydrogels((a) Rhodamine B stained hydrogels; (b) Original and stained hydrogels were spliced together;(c) Spliced hydrogels was placed for 2 h; (d) Tweezers Picked up the self-healing hydrogels; (e) Measured the diameter of the self-healing hydrogels; (f) Stretched the self-healing hydrogels)
图 6 OSA-CMCS水凝胶的黏弹性能((a)储能模量(G′)和损耗模量(G″ )随应变变化；(b) G′和G″ 随频率变化)
Figure 6. Viscoelastic properties of OSA-CMCS hydrogels((a) Storage modulus (G′) and loss modulus (G″ ) changed with strain; (b) G′ and G″ changed with frequency)
图 8 OSA-CMCS水凝胶的体外降解图(PBS、37℃)
Figure 8. In vitro degradation of OSA-CMCS hydrogels (PBS, 37℃)
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