Construction And Controlled Release Of Traditional Chinese Medicine Active Small Molecule Microcapsules Based On Pickering Microemulsion Template

Pickering emulsion,as a new slow-release drug carrier,can improve the stability and bioavailability of loaded drugs,and can also be directly used as a soft template to prepare microcapsules loaded with active functional small molecules,which is widely used in food,pharmaceutical,cosmetic and agricultural fields.Apigenin and resveratrol are small molecules of traditional Chinese medicine active monomers extracted from the root of hemsley and resveratrol respectively,with anti-cancer,antioxidant,anti-inflammatory and other biological activities.However,due to their poor water solubility and fat solubility,they are difficult to be absorbed by digestive tract mucosa and low oral bioavailability,which limits their application in many fields.Therefore,the development of green and intelligent Pickering emulsions or microcapsules loaded with apigenin and leuveratrol is of great value to expand its application in the fields of health food,medicine and cosmetics.In this paper,we prepared W/W and O/W Pickering emulsions using astragalus polysaccharide iron（III） nanoparticles and thermosensitive modified chitosan nanoparticles as phase stabilizer,respectively,and investigated their solubilization and encapsulation effects on resveratrol and apigenin.At the same time,the Pickering emulsions were used as templates to cross-link through simple ion and p H regulation.The microcapsules containing resveratrol and apigenin were prepared.Specific research results are as follows:（1）Study on solubilization and stability of Astragalus Polysaccharide Iron（III）complex W/W Pickering emulsion on active small molecules of two traditional Chinese medicinesThe application of small molecules of polyphenols and flavonoids in traditional Chinese medicine is limited due to poor water solubility and instability.Using delivery system to improve its bioavailability is a key research direction.In this part,Astragalus polysaccharide（APS）iron（III）nanoparticles and polydopamine nanoparticles were used as phase stabilizer to construct the W/W Pickering emulsion of APS/PEG,and investigate the effects of the emulsion system on the water solubility and stability of resveratrol and apigenin.The results showed that the W/W Pickering emulsion prepared with APS-Fe（Ⅲ）complex as stabilizer could significantly improve the solubility of resveratrol and apicin.Fluorescence microscopy showed that the resveratrol dispersed in W/W Pickering emulsion changed from undissolved fine acicular crystals to round droplets with the increase of APS-Fe（Ⅲ）dosage.Compared with the solubility of resveratrol and apigenin in pure water,the solubilization effect of W/W Pickering emulsion on resveratrol and apigenin reached 94%and 65%.Moreover,the photostability of resveratrol was obviously improved by embedding resveratrol in the W/W emulsion.In vitro antioxidant tests showed that APS-Fe（Ⅲ）complex stabilized W/W emulsion had strong antioxidant activity.The emulsion system also showed slow release of resveratrol and apigenin,and the release process was consistent with the first-order kinetic model.Skin absorption was measured in vitro using Franz diffusion cell and pig skin. Compared with resveratrol control solution based on 20%v/v ethanol,Pickering emulsion allowed higher skin retention and lower resveratrol penetration.This property makes the emulsion system containing resveratrol expected to be used in sunscreen cosmetics.（2）Preparation and properties of temperature-sensitive modified CS stabilized Pickering microemulsionIn this part,the p H and temperature sensitive CS-PNIPAM nanoparticles were prepared by radical initiation grafting polymerization,and O/W Pickering emulsion was prepared by using the nanoparticles as phase stabilizer.Oil and water separation and emulsification can be reversibly achieved by cycling p H from 5.0 to 9.0 or temperature from 25℃to 45℃.On this basis,the Pickering emulsion loaded with resveratrol was prepared by in-situ dissolution of resveratrol with clove essential oil.The properties of CS-PNIPAM stabilized Pickering emulsion loaded with resveratrol were measured.The results showed that Pickering emulsion could effectively prevent the oxidative decomposition of resveratrol.A small amount of emulsion on DPPH,ABTS free radical scavenging ability can reach more than 90%,has a strong antioxidant capacity.In vitro release indicated that the emulsion system was temperature sensitive to resveratrol release.The antibacterial experiments showed that the emulsion system has strong inhibitory effect on aspergillus Niger,Staphylococcus aureus and Escherichia coli.Compared with unencapsulated clove essential oil,Pickering emulsion has good antibacterial effect.This property makes the emulsion system can be effectively applied in food industry and cosmetics as an antiseptic component.（3）Study on p H regulation,preparation and release of Ca²⁺cross-linked Pickering microemulsion capsulesO/W Pickering emulsion stabilized by CS-PNIPAM nanoparticles was used as template to construct microcapsules loaded with resveratrol by adjusting p H value.FTIR results showed that resveratrol dissolved in clove essential oil was successfully loaded into the microcapsules.The encapsulation rate of CS-PNIPAM-PE microcapsules for resveratrol was73.77%±0.77.Microcapsules loaded with apigenin and resveratrol were prepared by Ca²⁺crosslinked APS-Fe（Ⅲ）stabilized W/W Pickering emulsion.The effects of Ca²⁺ concentration and sodium alginate concentration on the encapsulation of resveratrol and apigenin in microcapsules were investigated.The results showed that the concentration of sodium alginate was 2.0wt%.When the concentration of Ca Cl₂ solution was 1.5wt%,the encapsulation rates of resveratrol and apicin in microemulsion capsules were 80%and 73%.In addition,the release and antioxidant activity of two kinds of micromilk capsules were studied in vitro.The results showed that microencapsulation improved its stability and had strong antioxidant activity against DPPH and ABTS free radicals.Meanwhile,microcapsules with controllable release of resveratrol and apigenin were obtained.These results indicate that Pickering emulsion template is an effective method to construct microemulsion capsules and can be used as a promising carrier material.In conclusion,APS-Fe stabilized W/W Pickering emulsion and its microemulsion capsule can not only improve the solubility of insoluble drug molecules resveratrol and apigenin,achieve the slow release of resveratrol and apigenin,but also enhance the skin delivery of resveratrol,so they have potential contribution to green and sustainable cosmetics.Resveratrol Pickering emulsion and its microemulsion capsules stabilized by CS-PNIPAM showed excellent slow release and light protection for resveratrol,opening up new potential for the application of unstable active ingredients in food and agriculture.These findings are conducive to the development and utilization of other insoluble active small molecules and have broad application prospects in the field of delivery and slow release of bioactive substances.