Fabrication,Characterization And Utilization Of Peptide-Based Low Molecule Weight Hydrogel As Food Grade Delivery Systems

In recent years,peptide-based low molecular weight hydrogels（PLMWHGs）have been used as novel biomaterials in many fields due to the excellent physical,chemical,biological properties and the outstanding structural adjustable characteristics.However,the difficulty of controlling gelling mechanism and gelling process limit further application of PLMWHGs.Therefore,phenylalanine dipeptide with self-assembly characteristics as building blocks and active groups to design low molecular weight peptides were introduced to clarify the gelling mechanism and provide novel ideas for expansion and development of PLMWHGs.The PLMWHGs and composite hydrogel were fabricated filled gel delivery systems for food.The rheological and gelling properties of peptide-based hydrogels and composite hydrogels were measured by rheological tests to provide theoretical support for their application in the food industry.The loaded properties and protective effect on nutritional factors of filled gels were evaluated,the nutritional factors release behavior and mechanism from filled gel delivery systems were explored,which provided theoretical support for the application of LMWPHGs in food.The main results are as follows:（1）Three PLMWHGs with Ac SFFNH₂,Ac TFFNH₂,and YAFAF were successfully fabricated by solvent dilution method according to physical and chemical properties of several designed low molecular weight peptides.These three gelators have good thermal stability and no cytotoxicity.The molecular mechanisms of Ac TFFNH₂and YAFAF were verified using NMR and spectroscopy that were self-assembling supramolecular structures driven byπ-πstacking and hydrogen bond.The three-dimensional nanofiber network of PLMWHGs formed by fiber bundle cross-linking were observed using electron microscopes.When the solvent ratio was in the range of 0.1-0.2,Ac TFFNH₂ nanofibers were grooved,and YAFAF nanofiber was shaped as beaded.The rheological analysis showed that concentration of stock solution and temperature had significant impacts on gelling.Temperature is the main factor affecting the gelling behavior of hydrogels.Ac TFFNH₂hydrogels’gelling temperature were between11-13°C with different concentrations.YAFAF has self-assembly on intermolecular at room temperature,and decreasing temperature could promote the gelling process.The fiber crosslinking density depended on the concentration of peptides and was related to strength of hydrogels.As the same preparation conditions and same concentration,the strength of Ac TFFNH₂and YAFAF hydrogels were 862.15±18.43 and 1322.74±4.96 Pa,and their water contents were 99.46±0.68%and 99.48±0.42%,respectively,and the water holding capacity was both higher than 190%.The wet based hydrogels had anti swelling capacity,while the dry based hydrogel has better water absorption and retention capacity.According to the comparison in conditions with different p H values,temperatures and enzyme existed environment,YAFAF hydrogel was more stable than Ac TFFNH₂ hydrogel.However,Ac TFFNH₂ hydrogel was more stable and better self-healing capacity with shear frequency range of food industry.The PLMWHGs could be applied in food industry with suitable gel properties.（2）The composite hydrogels（TSG,YSG）were fabricated by mixing low molecular weight peptides with sodium alginate（SA）.The concentration of peptide in the composite hydrogel was higher than 3 mg/m L,which can form first cross-linked hydrogels.The intermolecular crosslinking of SA to reduce the volume and enhance strength of composite hydrogels.It was observed that the composite network of TSG was formed by peptide nanofiber wrapped by SA,and the composite dual-network of YSG was crossed by fibers of peptide and chambers of SA.TSG displayed a good self-healing capacity,while poor self-healing capacity of YSG.As the same formular,the strength of TSG,YSG were 4351.23±6.82 and 26302.8±91.03 Pa,and the water contents were 99.53±0.61%and 99.52±0.23%,respectively,and their water holding capacities were higher than those of the corresponding peptide-based hydrogels.The wet composite hydrogels swelled in both buffer solution and deionized water,while the dry composite hydrogels had good adsorption and retention ability to buffer solution and water,and the swelling rate is higher than the corresponding peptide-based hydrogels.In acidic/alkaline solution,high-temperature,and enzyme existed solution,SA could protect the gel network of peptide,and the strength and morphology of composite hydrogels were more stable.The strength and stability of composite hydrogels was improved by compounding with SA.（3）Filled hydrogel loading systems were prepared to load nutrients of different water-soluble.The load capacity and strength of filled hydrogel loading systems were enhanced with the increasing of nutrient concentration,but were limited by the stability of gel network or diffusive equilibrium.Compared with free nutrients,encapsulation could protect the activity of them.The releasing behavior of filled hydrogel loading systems during the simulated gastric and intestinal tracts digestion in vitro were influenced by p H value of solutions.By fitting several release kinetic models,releasing curves of nutrients from filled hydrogel loading systems were only related to accumulative time of releasing or concentration of nutrients because of high correlation coefficients of fitting with zero order release equation or first order release equation.The releasing mechanism were jointly controlled by diffusion and dissolution.Based on the releasing behavior and stability of filled hydrogel loading systems,they could be used as delivery materials for targeted releasing of nutrients in the small intestine.In conclusion,the peptide-based hydrogels designed and fabricated in this paper had basic hydrogel properties.The composite hydrogels combined with alginate improve gel strength and solvent retention ability,and had potential application in the field of food.Based on the releasing behavior and stability of the filled hydrogel,the encapsulation system of YAFAF hydrogels and composite hydrogel was able to small intestine-specified releasing of nutrients.