Microemulsion-polysaccharide Supramolecular Self-assembled Polyphenol Carrier

With the close attention to natural polyphenols in recent years,several new pharmacological activities of apigenin（API）and curcumin（CUR）,such as anti-inflammatory,antioxidant,anticancer and antiviral,have been gradually realized.Because of their low toxicity and less apparent side effects,API and CUR have attracted more attention.However,due to their flavonoid structures,the water solubilities of API and CUR were very low,leading to a limited clinical use and therapeutic value.Recently,intelligent drug delivery systems have been developed.In general,they can release drugs responsively according to the physiological environment,thus improving the bioavailability of drugs and reducing side effects.It has been found that microemulsion as a nanoscale self-assembly for drug delivery,can improve drug permeability.Natural polysaccharides have been widely used in food and pharmaceutical products,because of their good biocompatibility and biodegradability.Inthispaper,thepreparationandpropertiesof microemulsion-polysaccharide supramolecular self-assembly as the carrier of API/CUR were studied.The main research contents are summarized as follows:Firstly,the preparation and properties of hydroxypropyl-β-cyclodextrin（HP-β-CD）modified microemulsion as the carriers of API and CUR were studied.The API/HP-β-CD inclusion complex at molar ratio of 1:1 was prepared by the solvent-freeze-drying method and characterized by TGA,DSC,FT-IR,PXRD and ¹H NMR.The CUR/HP-β-CD inclusion complex was also prepared and characterized as a control.To further increase the solubility of polyphenols,the complex of HP-β-CD with food-grade cosurfactant-free microemulsion was constructed.The aqueous solubilities of polyphenols significantly increase in the HP-β-CD/Microemulsion complex,via solubilizing dominantly into the‘‘palisade’’layer,minor outer phase and inner core.The HP-β-CD modified microemulsion improves the cumulative percentage of polyphenols released.Moreover,polyphenols loaded in microemulsions with HP-β-CD had a higher antioxidant activity than that without HP-β-CD.Secondly,the preparation and properties of pH-sensitive microemulsion-filled gellan gum hydrogels as the carrier of API were studied.Several O/W microemulsions were constructed in Tween 40/S1570/coconut oil/glycerol/H2O system to solubilize API.Then these API-loaded microemulsions were incorporated into gellan gum hydrogels to obtain the composite hydrogels encapsulated API（API-Me-Gels）.In vitro release studies resulted that the composite hydrogels could control the drug release under acidic（pH 1.2）and weak alkaline conditions（pH 7.4）.This was due to the increase of crosslinking degree under acidic medium and degradation under weak alkaline medium,observed by SEM and FT-IR analysis.The in vitro release kinetics resulted that the release under acidic conditions was a Fickian diffusion-controlled mechanism.While the in vitro release under weak alkaline condition was erosion-controlled mechanism.In addition,the gellan gum/sodium hyaluronate and gellan gum/sodium caseinate composite hydrogels were further studied.The CUR-loaded microemulsions were incorporated into the composite hydrogels to obtain the microemulsion filled composite hydrogels encapsulated CUR（CUR-Me-Gels）.The effects of composite ratio of polymers and GDL content on the structures and in vitro release behaviors of CUR-Me-Gels were also explored.As a result,the microemulsion-filled hydrogels could be a promising pH-controlled release system for oral delivery of polyphenols.Finally,the formation and dynamics of supramolecular self-assemblies were studied by mesoscopic dynamics（MesoDyn）and dissipative particle dynamics（DPD）simulation.The mesoscopic model（C₂E₃）of nonionic surfactant Brij97 was first proposed.The structural transition between O/W and bicontinuous microemulsion formed by Brij97/isopropanol/isoamyl acetate/H₂O system was successfully predicted by MesoDyn simulation.In addition,the coarse-grained model of Brij97 was proposed,and the formation and structure transition of lyotropic liquid crystals in Brij97/H₂O binary system were successfully simulated by DPD simulation.The effect of isopropyl myristate（IPM）content on the structure of layered liquid crystals was studied.In addition,the dynamic formation process of microemulsion formed by Tween 80/isoamyl acetate/H₂O system was also studied by DPD simulation.These results provide some theoretical guidance for constructing supramolecular self-assembly as a drug carrier.