Digestive Characteristics Of Liposomes With Different Wall Materials And Core Materials And The Effect On Caco-2 Cells

Liposome,usually formed by amphiphilic molecules and in which the hydrophobic tail of the amphiphilic molecules gather together and the hydrophilic head is exposed to the aqueous phase,is a self-assembling and cell-resembling delivery system with bilayer structure.With their unique properties such as protection,targeting,control release and non-toxic,liposomes have shown great potential application potential in medicine,cosmetics and foods as a microcapsule.Phospholipids,the main wall material of liposomes,have the different structure which can influence the physical-chemical properties and digestion stability of liposomes.Lactoferrin(LF),a protein with multiple biological activity,has ability of antibacterial,antioxidant,antiviral,immunomodulatory and transport of iron ions,and has been widely used as a food nutrition fortifier.The natural polyphenols quercetin(QUE)and resveratrol(RES),with the ability of antioxidant,antibacterial,hypotensive,hypolipidemic and protecting the cardiovascular and so on,have been widely used in health care products and functional foods.However,it is generally recognized that LF is easily hydrolyzed by the enzymes in the GI tract,and QUE and RES are susceptible to temperature,pH and other factors which could reduce its biological activity and affect its absorption and utilization of the body.Therefore,we intended to explore the gastrointestinal digestion behavior of LF-loaded liposomes(LF liposomes)with different wall phospholipids(different fatty acid chain length,fatty acid saturation and head group,respectively)by analyzing the average particle size,particle distribution,Zeta potential,surface microcosmic characteristics,core release rate,and the structure of phospholipid bilayer.In addition,we investigated the gastrointestinal digestion properties of liposomes with different core materials(QUE,RES),as well as the effects of different concentrations of bile salts(without pancreatins)on the structure of QUE liposomes and RES liposomes under the small intestine condition.Moreover,the cellular uptake amount of QUE/RES liposomes and the effect on Caco-2 cytotoxicity were studied.The results were summarized as following:(1)Digestion behavior of liposomes with different wall materialsThe z-average diameter of liposomes with different fatty acid chain length(C16,C18,C20),fatty acid saturation(0,1,2,3)and head group(PA,PC,PE,PI>were about 300±61 nm,700±42 nm,400±34 nm,300±79 nm,700±42 nm,200±76 nm,300±25 nm,700±42 nm,800± 10 nm,400 ± 50 nm,600 ± 69 nm,respectively.The results showed that the particle distribution,membrane structure of the liposomes with different wall structure was less influenced and the liposomes were stable to protect the entrapped LF from pepsin hydrolysis during SGF digestion.In SIF,the particle average diameter,surface charge,morphology and LF release of liposomes were changed more obviously owing to trypsin and bile salts,which are well known for their ability to destabilize phospholipid bilayers.In addition,the results showed that the digestion behavior of liposomes with different fatty acid chain(16,18,20)were similar and the liposomes prepared from PC with the saturation fatty acid chain were relatively stable during gastrointestinal digestion.(2)Digestion behavior of liposomes with different core materialsThe z-average diameter of QUE liposomes and RES liposomes were about 1000 ± 78 nm and 1200 ± 62 nm,respectively.The encapsulation efficiency of the QUE and RES in the liposomes was about 78.06 ±0.02%and 85.12 ± 0.01%,respectively.The particle distribution,zeta potential and functional group structure of QUE liposomes and RES liposomes were little changed during SGF digestion.After digestion in SIF,the structures and functional groups of QUE liposomes and RES liposomes were damaged and the encapsulation efficiency of QUE and RES decreased to 30.00±0.5%or less.Moreover,the results indicated QUE liposomes were significantly affected by high bile salts concentrations.(3)Effects of QUE liposomes and RES liposomes on Caco-2 cellsThe cell inhibition and apoptosis rates of QUE/RES(80 ?M)were less than 15.00±0.5%and 20.00±0.5%,respectively.There was no significant difference compared to the control group,indicating that there were little or no toxicity on Caco-2 cells.In addition,the cell uptake of QUE/RES liposomes was obviously higher than that of QUE/RES without encapsulation.This thesis deeply studied the relationship between the structure of liposomal wall matereials/core molecules and the digestion behavior of liposomes,which provided a guide for the development of stable liposomes with specific properties under gastrointestional conditions.Besides,the cell toxicity and absorption efficiency of polyphenol liposomes were studied,and the technique could showed an example for other carriers and functional molecule during digestion.