Fabrication And Characterization Of The Delivery Systems For Curcumin On The Basis Of Nanostructured Lipid Carriers

Curcumin（Cur）has been reported to possess many health-benefiting,nevertheless,the low solubility,chemical stability,and bioavailability of Cur inhibited their utilization as functional ingredient in the food industry.Nanostructured lipid carriers（NLCs）represent an improved generation of lipid nanoparticles that combine the delivery advantages of other previous lipid carriers with the innovative use of a solid-liquid hybrid lipid as the lipid matrix,offering advantages that other carriers do not have and offering potential for the delivery of Cur.In this study,an"all-natural"Cur-NLCs stabilised by biomolecules was constructed using an interfacial engineering strategy,and based on this,Pickering emulsions,double cross-linked gels and gel microspheres were developed as delivery forms to broaden the application of NLCs in the food industry.The main findings and conclusions are as follows.（1）In this work,single layer NLCs（S-NLCs）stabilized by isolated whey protein alone were constructed.S-NLCs are spherical in shape,with a hydrodynamic diameter of approximately 300nm and a Cur encapsulation rate of less than 30%.These values were improved after the interfacial modification.Environmental stability experiments showed that the particle size of S-NLCs increased with increasing ion concentration and decreasing p H to approximately 1000 nm and 800 nm,respectively,while the particle size of D-NLCs increased to approximately 500 nm and 700 nm,respectively,under the same conditions,higher than the 400 nm of C-NLCs.faster interfacial adsorption rates(Kdiff=0.592 m N/m/s^1/2)and higher surface tension equilibrium values（～30 m N/m）,which are directly related to the stronger and more diverse types of interactions between their biopolymers.As a result,there is better inhibition of crystallographic evolution and higher stability of the loaded Cur in the C-NLCs.Simulated digestion experiments showed that both interfacial modifications reduced the degree of matrix fat hydrolysis（both below 50%）,while increasing the bioavailability of the core（approximately 60%）.（2）The results of the CLSM analysis showed that the conductivity of the S-NLCs-stabilized Pickering emulsions were all W/O emulsions,with an increasing trend of 0 to 3.67±1.55 us/cm with increasing proportion of NLCs.For the Pickering emulsions stabilized by D-NLCs and C-NLCs,the conductivity of Pickering emulsions increased to 144.33±41.06 us/cm and 83.00±10.81 us/cm with increasing the proportion of NLCs in the system,respectively,realizing the phase transition process from W/O to O/W.Pickering emulsions showed the highest storage stability（Cur retention of 88.45±1.01%and 57.15±3.93%at 4°C and 25°C storage conditions respectively）,centrifugal stability（with the lowest emulsion precipitation index）and thermal stability when 50%of D-NLCs were present.contact angle and surface tension analysis of NLCs and The steady-state rheological analysis of Pickering emulsions showed that D-and C-NLCs as amphiphilic particles have the ability to stabilise W/O and O/W emulsions,while the wettability of the nanoparticles as stabilisers and the denseness of their arrangement in the interfacial layer have an important influence on the stability of the emulsions.Simulated digestion experiments showed that the maximum lipolytic equilibrium value of Pickering emulsions did not exceed 15.26±0.76%,which was less than the minimum lipolytic equilibrium value of 17.53±0.30%for the control NLCs,due to gelling and the accumulation in the upper layer of the digest reducing the contact area of Pickering emulsions with the digest and lowering the lipolytic level of the emulsions,which provides an opportunity to develop Cur of NLCs-based retardants.（3）The microspheres were prepared by electrospraying and Ca²⁺cross-linking of C-NLCs with different concentrations of magnetic gelatine,and the results of SEM,CLSM and particle size analysis showed that the surface of the microspheres was rough and ellipsoidal in shape,and the particle size decreased from 231.67±2.82μm to 175.22±1.96μm with increasing concentration of magnetic gelatine.This is the result of both the viscosity and the electrical conductivity of the raw material solution.At the same time the microspheres showed magnetic response and thermal phase change behaviour with the dispersion Cur retention and step thermal thixotropic viscosity recovery close to 0%and 100%,respectively,under magnetic field conditions,with the responsiveness being additive to the magnetic gelatine.Analysis of the storage stability of the microspheres showed high structural stability during storage with Cur retention generally above 80%.The microspheres were sensitive to acidic p H and Na Cl concentration,and in vitro release tests demonstrated that Cur in microspheres has an S-shaped release profile,with the p H and Na Cl of the release medium influencing the release behaviour of Cur.（4）The effects of the combination of cross-linker concentrations on the gels were investigated by constructing GNP and Ca²⁺double cross-linked NLCs gels based on C-NLCs.SEM and CLSM results showed that the gel cross-link density was positively correlated with the cross-linker concentration and that the combination of the two cross-linkers was able to construct structurally homogeneous double cross-linked gels.Rheological and textural analyses of the viscoelasticity of the gels showed that Ca²⁺crosslinking provided the main structural support for the gel network.The water holding capacity of the gels,their freeze-thaw stability and their swelling under acidic and varying ionic strength conditions were influenced by the crosslinking density.Simulated digestions showed that the gels inhibited lipolysis of NLCs and achieved a slow release of Cur.