| Linseed oil and quercetin are both fat-soluble nutrients with low solubilities in water,resulting in low oral bioavailabilities.Lipid based micro-and nano-delivery systems can improve the solubility of fat-soluble nutrients in digestive solution and hence the oral bioavailability.Therefore,based on the traditional lipid based micro-and nano-delivery systems and food-grade raw materials,this paper studied micro-and nano-delivery systems for dietary supplement which were more stable,higher bioavailability,and more suitable for the aging intestinal tract.An aging animal model was established to study the absorption and utilization of micro-and nano-delivery systems,and to elucidate the differences of absorption between before and after carrier transformation and between normal and aging intestinal tracts.The main contents of this study are as follows:(1)Firstly,the preparation and evaluation of linseed oil and quercetin co-loaded nanoemulsions were discussed.Nanoemulsions were prepared by high pressure homogenization with particle size about 150 nm.In vitro antioxidant experiment showed that the co-loading of quercetin and linseed oil showed synergistic effect on antioxidant activity.In vitro digestion experiments showed that particle size had a great influence on the digestion and absorption of bioactives.Compared with traditional emulsions,the digestibility of linseed oil and the bio-accessibility of quercetin in nanoemulsions were greatly improved.Linseed oil in nanoemulsions had good oxidation stability.D-galactose method was used to establish intestinal aging rat model.In vivo intestinal perfusion experiment showed that nano-emulsification could enhance the absorption rate of both quercetin and linseed oil in intestinal mucosa.Nano-emulsification could reduce the effect of intestinal aging on the absorption of fat-soluble nutrients.Efficacy assessment showed that quercetin could reduce the oxidative damage caused by long-term consumption of linseed oil.The hypolipidemiceffect of quercetin combined with linseed oil was better than that of linseed oil alone.(2)Secondly,solid lipids were introduced to investigate the preparation and evaluation of linseed oil and quercetin co-loaded nanostructured lipid carriers(NLC).NLCs were prepared by hot-high pressure homogenization.The loadings of linseed oil and quercetin were 6% and0.3% respectively.The release of quercetin from NLC showed a sustained release effect.The addition of solid lipids could affect the bio-accessibility of bioactives.The digestion of lipids and the release of fat-soluble nutrients can be controlled by solid lipids.Linseed oil was loaded in semi-solid lipid cores and had less contact with reactive oxygen species in water.Compared with linseed oil nanoemulsions,NLCs had better protective effect on linseed oil.After diluted by 100 times,the cytotoxicity of NLCs was relatively low and had no effect on the growth of cells,so the application of NLCs was relatively safe.Pharmacokinetics results showed that NLCs could improve the oral bioavailability of quercetin.Compared with nanoemulsions,the addition of solid lipid could reduce the absorption rate of quercetin and achieve a sustained release effect,which ultimately improved the oral bioavailability of quercetin.(3)Thirdly,lipid based delivery system was solidified.The preparation and evaluation of linseed oil and quercetin co-loaded solid self-emulsifying delivery system(solid LQ-SEDS)were studied.Solid self-emulsifying delivery system was prepared by physical adsorption method.The solid LQ-SEDS prepared with liquid formulation/Aerosil 300 ratio of 2:1 had good flow properties.The digestion rate and degree of linseed oil were decreased after liquid LQ-SEDS adsorbed into Aerosil 300,which was attributed to the inhibiting effect of Aerosil300 on lipid decomposition.Quercetin in solid LQ-SEDS showed a slower release rate than that in liquid LQ-SEDS.In addition,compared with linseed oil emulsions,non-aqueous environment can slow down the oxidation of linseed oil.Histopathological study of small intestine in rats showed that solid LQ-SEDS could promote the absorption of fat-soluble nutrients without obvious damage to small intestinal mucosa.Cytotoxicity evaluation showed that solid LQ-SEDS had good safety after dilution.Solid LQ-SEDS water dispersions can improve the antioxidant activity of cells,prevent or reduce the damage caused by oxidative stress to cells to a certain extent,and protect cells.(4)Finally,secondary encapsulation was used to improve the stability of lipid baseddelivery system.The preparation and evaluation of linseed oil and quercetin co-loaded natural hydrogel beads were studied.Liposomes containing linseed oil and quercetin were loaded into chitosan hydrogel beads by an injection method combined with ion gelation.SEM showed that the prepared hydrogel beads had obvious three-dimensional network structure.When the liposomes were loaded into the hydrogel beads,the release of quercetin showed a sustained-release effect.With the increasing of chitosan concentration,the cross-linking density of hydrogel beads increased correspondingly,and the pore size of hydrogel beads decreased,resulting in the slow release rate of quercetin.In vitro simulated digestion experiment showed that the stability of liposomes in gastrointestinal solution could be improved by loading liposomes into hydrogel beads.Accelerated oxidation study and photostability experiment showed that the chemical stability of bioactives could be improved by loading liposomes into hydrogel beads.Through the above studies,the application bottlenecks of linseed oil and quercetin such as low water solubility,poor stability and low oral bioavailability were solved.The synergistic effects of their combination on stability,antioxidant and hypolipidemic effect were revealed.At the same time,the stability of traditional lipid based delivery systems was improved by solid lipid,solidification and secondary encapsulation,and the release of fat-soluble nutrients was further controlled to improve oral bioavailability.The animal model of intestinal aging was established to study the differences of absorption and utilization between before and after carrier transformation and between normal and aging intestinal tracts.Finally,it will provide some research value for the application of micro-nano delivery systems in the aging population to meet their health needs. |
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