The Preparation and Bioavailability of Curcumin Loaded Food Delivery System by pH-Driven Method
Author:Peng Sheng Feng
Polyphenol is the second largest naturally secondary metabolite.It is a nonnutritive active ingredient in fruits,vegetables,grains and other plant-derived foods and has a wide range of physiological activities.Some of these polyphenols are hydrophobic.The extremely low water solubility and poor stability during processing,storage and gastrointestinal environment,resulting in extremely low bioavailability.The method of encapsulating hydrophobic polyphenols in food delivery system is an effective way to overcome the above disadvantages.However,the existing preparation methods need to use organic reagents,and the preparation process is relatively complex and costly,which is not conducive to the application in food industry.Therefore,there is great interest to develop new methods that are simple,fast and suitable for the application in the food industry.This study can be devided into the following three parts.First,pH-driven method was used to prepare lipophilic polyphenols loaded liposomes.The advantage,disadvantage and application of pHdriven mehod were discussed.Then,lecithins with different composition and amphiphilic polymers were ustilized to prepare curcumin liposomes.The influence of liposomal mabrane composition on the formation,stability and bioavailability of curcumin liposomes were studied.Finally,the pH-driven method was used to prepare curcumin nanoparticles.The effects of nanoparticles on the stability and bioavailability of curcumin were investigated.The main contents are as follows:(1)The effects of three preparation methods(new pH driven method,traditional thin film method and ethanol injection method)on the stability and bioaccessibility of curcumin liposomes were compared.The transmission electron microscope confirmed that curcumin liposomes were successfully prepared by pH-driven method.The physical stability results showed that curcumin liposomes prepared by pH-driven method were unstable at high ionic strength but were relatively stable during storage without any curcumin leakage.The in vitro simulated digestion study showed that the curcumin bioaccesssbility of liposomes prepared by pH-driven method were equal to that of thin film method and higher than that of ethanol injection method.The pHdriven method has many advantages such as simple,fast,and does not require high temperature or organic solvents.In order to understand its application range,the pHdriven method is applied to prepare resveratrol and quercetin loaded liposomes.The results showed that all these polyphenols could be loaded into the liposomes by pHdriven method,but the encapsulation efficiency(EE)depend on their alkaline stability.Curcumin was stable in alkaline solutions,and the EE of curcumin liposomes was very high(100%);the alkaline stability of resveratrol was poor,but the EE of resveratrol liposomes was relavtively high(90%).However,quercetin has a very poor alkaline stability,and the EE of quercetin liposome was only 56%.There are huge loss during pH-driven process.Therefore,the pH-driven method is not suitable for the preparation of quercetin carrier system.(2)Firstly,curcumin liposomes were prepared by microfluidizer method combined with pH driving method,and the effects of phospholipid composition on liposome stability and curcumin loading were compared.The transmission electron microscope and confocal laser scanning microscopy results showed that the curcumin liposomes with a small unilamellar vesicle structure were successfully obtained.These liposomes were highly stable,and the purity of phospholipids had no effect on the stability.Even low purity phospholipids could be used to prepare high stable curcumin liposomes.The encapsulation efficiency and stability of curcumin in liposoems were proportional to lecithin purity.Finally,the effects of amphiphilic polymers on liposome stability and cell uptake rate were investigated.The microstructure and membrane fluidity results showed that hybrid liposoems composed of amphiphilic chitosan and lecithin were successfully prepared.Compared with phospholipid liposomes,the hybrid liposomes displayed better storage stability and more sustained curcumin release.Cellular uptake experiments showed that the hybrid liposomes significantly increased the bioavailability of curcumin.(3)A simple and rapid pH-driven method was applied to prepare small amphiphilic molecules(tea saponin and sophorolipid)and large amphiphilic molecules(casein,whey protein isolate,soybean protein isolate and gum Arabic)coated curcumin particles.The formation mechanism,physical and storage stability,and in vitro and in vivo bioavailability were explored.Results show that during the pH-drive process,curcumin molecules convert from hydrophilic form to hydrophobic form,it recrystallization into nanocrystal nucleus.If there are amphiphilic molecules in the systems,these molecules would absorbed onto the surface of curcumin crystal nucleus driven by hydrophobic forces.Then,the nanocrystal nuclesus could not growth into curcumin crystals and amphiphilic molecules coated curcumin particles were frabricated.Physical stability tests showed that the physical stability of curcumin particles depended on the amphiphilic molecules.For example,tea saponin was unstable at low pH and high ion concentration,while casein flocculated and precipitated at its isoelectric point and low calcium ion concentration.The amphiphilic macromolecular coated curcumin particles have poor thermal stability and storage stability,so as to desorption and form curcumin crystal precipitation.The in vitro digestion model and rat study showed that amphiphilic small molecules could significantly improve the in vivo and in vitro bioavailability of curcumin.