胞外多糖/9-芴甲氧羰基-苯丙氨酸复合水凝胶药物缓释体系构建  

Development of a Exopolysaccharides/9-Fluorenylmethyloxycarbonyl-phenylalanine Hydrogel System for Drug Delivery

作　　者：张艺华 刘闪闪 李妍[1] 李怀印 马鑫毅 耿伟涛 ZHANG Yi-hua;LIU Shan-shan;LI Yan;LI Huai-yin;MA Xin-yi;GENG Wei-tao(College of Food Science and Engineering,Tianjin University of Science and Technology,Tianjin 300457,China)

机构地区：[1]天津科技大学食品科学与工程学院,天津300457

出　　处：《高分子通报》2024年第10期1438-1447,共10页Polymer Bulletin

基　　金：天津市大学生创新创业训练计划(项目号202310057247)。

摘　　要：报道了一种新型肽-多糖水凝胶作为潜在亲水药物载体,并研究了其物理特性和药物释放性能。利用9-芴基甲氧羰基-苯丙氨酸(Fmoc-F)在胞外多糖(EPS)溶液中完成分子自组装,制备了EPS含量分别为33%、50%和66%的三种Fmoc-F/EPS水凝胶,命名为EPS33、EPS50和EPS66。通过流变、扫描电镜和质构分析表征了EPS对水凝胶结构、形态和机械性能的影响;通过傅里叶变换红外光谱探究了水凝胶中的多糖和多肽的结合方式;通过溶血实验、自由基清除实验、罗丹明B的载药量和体外释放性能,确定了EPS对水凝胶的安全性、抗氧化能力和亲水药物的递送能力的影响。结果表明含不同比例EPS的Fmoc-F/EPS水凝胶均表现出凝胶弹性固体行为,且EPS的增加使水凝胶的网络孔径增大;EPS的-OH通过和Fmoc-F分子之间形成了氢键相互作用。与Fmoc-F相比,EPS66的硬度降低,为1.689 g;对罗丹明B的载药量增加了22.79%,达到259.8 mg/mL;24 h穿透猪皮肤的深度增加了20.15%,达到1576.5μm。因此,双歧杆菌EPS可以通过与Fmoc-F的氢键相互作用形成具有更大网络孔径的稳定水凝胶,并赋予水凝胶更强的亲水药物装载能力。通过调整EPS的比例可以制备载药量大、抗氧化和控释效果良好、生物安全性好的可用于皮肤亲水性药物递送应用潜力的新型肽-多糖水凝胶。This study introduces a new peptide-polysaccharide hydrogel for drug carriers,exploring its physical properties and drug release capabilities.Three variations of hydrogel EPS33,EPS50 and EPS66 with exopolysaccharides(EPS)contents of 33%,50%and 66%,respectively,were created using different ratios of 9-fluorenylmethoxycarbonyl-phenylalanine(Fmoc-F)to EPS.The influence of EPS on the structural,morphological,and mechanical characteristics of hydrogels was assessed using rheological,scanning electron microscopy,and textural analyses.The interaction between EPS and Fmoc-F within the hydrogels was examined by Fourier Transform Infrared(FTIR)spectroscopy.Furthermore,the effects of EPS on the biocompatibility,antioxidant properties,and drug delivery capabilities of the hydrogels were evaluated via hemolysis,free radical scavenging,drug loading,and in vitro release profiling using rhodamine B.The findings indicated that the Fmoc-F/EPS hydrogels with varying ratios of EPS displayed characteristics of gelelastic solid behavior,with an observed increase in the network pore size with higher EPS content.The―OH groups of EPS were found to establish hydrogen-bonding interactions within and between Fmoc-F molecules.Compared to Fmoc-F,the hardness of EPS66 decreased to 1.689 g,and the loading capacity of rhodamine B increased by 22.79%to 259.8 mg/mL.The penetration depth through pig skin increased by 20.15%within 24 h,reaching 1576.5μm.Therefore,it was demonstrated that Bifidobacterium EPS can create a stable hydrogel with a larger network pore size by engaging in hydrogen bonding interactions with Fmoc-F,resulting in an enhanced hydrophilic drug loading capacity.By manipulating the EPS ratio,novel peptidepolysaccharide hydrogels can be developed with superior drug-loading capacity,antioxidant properties,release capabilities,and biosafety,making them suitable for applications in skin hydrophilic drug delivery.

关 键 词：自组装 肽-多糖水凝胶 药物载体 胞外多糖 药物缓释 

分 类 号：TQ460.4[化学工程—制药化工] TQ427.26