Preparation of hexanoyl ethylene glycol chitosan/poloxamer composite hydrogel for drug release
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摘要: 为减少泊洛沙姆水凝胶的溶胶-凝胶转变温度对浓度的依赖性，以泊洛沙姆(P407)为基材，将己酰化乙二醇壳聚糖(HGC)与泊洛沙姆复合，制备了己酰化乙二醇壳聚糖/泊洛沙姆(HGC/P407)复合水凝胶，利用FTIR、SEM及试管反转法探讨了HGC/P407复合水凝胶的性能，并利用紫外-可见分光光度计(UV-vis)对HGC/P407复合水凝胶的体外药物缓释性能进行表征。结果表明，通过控制HGC的加入量，基于3%泊洛沙姆的HGC/P407复合水凝胶即可发生溶胶-凝胶转变现象，并使HGC/P407复合水凝胶的溶胶-凝胶转变温度处于32~37℃。HGC/P407复合水凝胶具有高度孔隙率，孔隙之间相互连通，孔径大小处于10~90 µm的范围之内。HGC/P407复合水凝胶对抗癌药物吉西他滨的释药量达到82.4%~90.6%，缓释时间可达80 h左右。HGC/P407复合水凝胶在可注射药物载体领域具有重要的应用前景。Abstract: In order to reduce the dependence of the sol-gel transition temperature of the poloxamer hydrogel on the concentration, the poloxamer (P407) was used as the substrate, and hexanoyl ethylene glycol chitosan (HGC) was compounded with poloxamer to prepare HGC/P407 composite hydrogel. FTIR, SEM and tube inversion method were used to investigate the properties of HGC/P407 composite hydrogel in different mass ratios, and the in vitro drug release performance of HGC/P407 composite hydrogel was characterized by UV-vis spectroscopy. The results show that sol-gel transformation can occur in HGC/P407 hydrogel based on 3% poloxam by controlling the addition of HGC, and the sol-gel transition temperature of HGC/P407 hydrogel is between 32℃ and 37℃. HGC/P407 composite hydrogel has high porosity with interconnected pores which size ranging from 10 to 90 µm. The release amount of the anticancer drug gemcitabine of HGC/P407 composite hydrogel is 82%~90.6%, and the sustained release time can reach about 80 h. HGC/P407 composite hydrogel has important application prospects in the field of injectable drug carriers.
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Key words:
- hexanoyl glycol chitosan /
- poloxamer /
- composite hydrogel /
- drug release /
- injectability
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图 1 己酰化乙二醇壳聚糖(HGC)的合成路线
Figure 1. synthetic route of hexanoyl ethylene glycol chitosan (HGC)
图 2 乙二醇壳聚糖(GC)与HGC的核磁共振氢谱图(a)和FTIR图谱(b)；试管反转法测定的HGC溶胶-凝胶转变相图(c)
Figure 2. 1H NMR (a) and FTIR spectra of glycol chitosan (GC) and HGC (b); Sol-gel transition phase diagram of HGC measured by tube inversion method (c)
图 3 HGC/P407复合水凝胶、P407及HGC样品FTIR图谱
Figure 3. FTIR spectra of HGC/P407 composite hydrogel，P407 and HGC
图 4 试管反转法测定的HGC/P407复合水凝胶的溶胶-凝胶转变相图
Figure 4. Sol-gel transition phase diagram of HGC/P407 measured by tube inversion method
图 5 70%HGC/P407 (a)和100%HGC/P407 (b)复合水凝胶的温度依赖性流变行为
Figure 5. Temperature dependent rheological behavior of 70%HGC/P407 (a) and 100%HGC/P407 (b) composite hydrogel
G′—Storage modulus; G″ —Loss modulus
图 6 70%HGC/P407复合水凝胶25℃环境中照片(a)及染色后可注射性图示(b)；(c)通过注射针头注射入37℃模具内；(d) 37℃时的凝胶形态
Figure 6. 70%HGC/P407 composite hydrogel in 25℃ environment (a) and injectability diagram after staining (b); (c) Injection into 37℃; (d) Mold through injection needle with the gel morphology at temperature 37℃
图 7 70%HGC/P407 (a)和100%HGC/P407 (b)复合水凝胶的频率依赖性流变行为
Figure 7. Frequency sweeps of 70%HGC/P407 (a) and 100%HGC/P407 (b) composite hydrogel
图 8 HGC/P407复合水凝胶的横截面形貌的FE-SEM图像
Figure 8. FE-SEM images of the cross-sectional morphology of HGC/P407 composite hydrogel
图 10 HGC/P407复合水凝胶的体外药物释放性能
Figure 10. In vitro drug release performance of HGC/P407 composite hydrogel
表 1 HGC/泊洛沙姆407 (P407)复合水凝胶的配方
Table 1. The formula of HGC/poloxamer (P407) composite hydrogel
Samples Mass ratio Temprerature/℃ 30%HGC/P407 0.3∶1 65 50%HGC/P407 0.5∶1 50 70%HGC/P407 0.7∶1 37 100%HGC/P407 1.0∶1 32 
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表 2 HGC/P407复合水凝胶对吉西他滨的释放机制
Table 2. Release characteristics of encapsulated gemcitabine from HGC/P407 composite hydrogels
Samples K n Transport mechanism 70%HGC/P407 0.68 0.16 Pseudo-Fickian 100%HGC/P407 0.65 0.12 Pseudo-Fickian Notes: K ─ Rate constant; n ─ Release index.
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