Construction And Properties Of Edible Cyclodextrin-based Metal-organic Framework Nanocarriers

Metal-organic frameworks（MOFs）are a new kind of self-assembled porous material based on metal coordination principle,it has unique structural properties,such as a high surface area,highly porous topology,and tunable size.However,the long preparation period,high cost,complex preparation process and the use of transition metals limit the application of MOFs in food and medicine.It is an urgent problem to develop a safe,non-toxic,biocompatible and easily absorbed bioactive ingredient nano-carrier,and verify its feasibility as a biological active ingredient carrier.It is of great significance to expand the application scope of MOFs and solve the problems of poor solubility and low absorption rate of effective ingredients in food and biomedicine.The main results are shown as follows:（1）This study successfully conducted the rapid synthesis of highly porous cyclodextrin metal–organic frameworks（S-CD-MOF）based on the theory of seed induction.A new method for the preparation of CD-MOF by seed induction base the theory of crystal nucleation and growth was developed.The preparation period was shortened from over 24 to 6 h,and the size of CD-MOF crystals decreased from（6.2±0.8）μm to（1.8±0.4）μm.The crystal structure,thermal characteristics and cytotoxicity were investigated,and the results showed that the S-CD-MOF crystal structure remained intact,with higher crystallinity,thermal stability and N₂adsorption.The cytotoxicity test showed that S-CD-MOF was safe,nontoxic and had good biocompatibility.（2）The size control strategy of S-CD-MOF was constructed.The size of S-CD-MOF can be regulated by adjusting the supersaturation of the solution and controlling the crystal precipitation rate.It was found that the crystal size of S-CD-MOF could be significantly reduced by controlling the crystallization time and selecting ultrasonic assistance.The morphology,crystal structure,thermal properties and N₂ adsorption properties of S-CD-MOF with different sizes were investigated.The results showed that the controlled preparation of S-CD-MOF crystals with average particle size 200 nm,500 nm and 2μm could be realized by controlling the preparation conditions.Moreover,the crystallinity and N₂ adsorption capacity of S-CD-MOF were further improved in a shorter time.（3）The loading of S-CD-MOF on the hydrophobic active component was investigated.Nile red（NR）was chosen as the hydrophobic molecule model and resveratrol was chosen as the hydrophobic active component,the loading and interaction rules of S-CD-MOF on hydrophobic molecules were investigated.The fluorescence spectrum results showed the formation of a 1:1 complex between NR and S-CD-MOFs.Moreover,S-CD-MOF has a higher affinity constant K value than CD,demonstrating the potential of S-CD-MOFs as carriers for hydrophobic drug delivery applications.The fluorescence spectrum analysis results showed that the complex was driven by hydrophobic interactions.Furthermore,the loading of S-CD-MOFs on resveratrol significantly improved its stability and slow-release effect.（4）S-CD-MOF/chitosan nanocapsules with core-shell structure were prepared and its loading behavior was investigated.Due to the positive charge characteristic of chitosan,it was deposited on the surface of S-CD-MOF by electrostatic interaction,and the nanocapsule with hydrophobic core and hydrophilic chitosan shell was formed.The presence of the CS coating improved dispersion of nanocapsules,which was attributed to their ability to inhibit particle aggregation.Moreover,the encapsulation efficiency of resveratrol within the nanocapsules increased significantly after coating them with chitosan（from 66.5 to 91.3%）,the complex was driven by a combination of hydrophobic,hydrogen bonding,and van der Waals interactions.The chitosan coating was also shown to increase the antioxidant activity and photostability of the encapsulated resveratrol.This study solved the problem of poor dispersion of S-CD-MOF in water environment.（5）The loading and interaction of CD-MOFs on hydrophilic active component-glycyrrhizic acid（GA）was investigated.The results showed that the maximum amount of GA bound to the S-CD-MOF was around 850μg/mg,this amount was higher than has been reported so far.This is mainly because GA not only interacts with the cavity of CD,but also has a large number of hydroxyl groups in the porous structure of S-CD-MOF space network,which also provides better embedding effect.The infrared analysis results showed that the combination of S-CD-MOF and GA was mainly hydrophobic interaction,hydrogen bond and van der Waals force.（6）The emulsion delivery system was constructed based on S-CD-MOF,GA and edible oil as main components,and its digestibility and transfer performance of active ingredients were investigated.The emulsions’transitions from sol to gel could be controlled using different oil fractions and mass ratios of CD-MOF and GA.The mechanisms for the emulsion gel formation were revealed by the rheological and LF-NMR results.The rheological results showed that the G’of the emulsions was obviously higher than G"when the oil fraction was higher than 0.3 at the 1:3 mass ratio of CD-MOF and GA,indicating the formation of elastic gel networks.The LF-NMR results showed that the T₂₂ relaxation time of the emulsion decreased when the oil fractions increased from 0.1 to 0.6,which indicated that the movable water was converted into constructral water,confirming the transition from emulsions to emulsion gels.The emulsion gels showed good stability even in high-alkaline pH and high temperature conditions.After standard simulated digestion,the lipid droplets were almost completely digested and resveratrol was released,with a high bioacceptability of 73.8%,indicating that the emulsion could be used as an effective resveratrol delivery carrier.