Effects Of Three Oral Delivery Systems On The Absorption Of Astilbin In Rats

Flavonoids are a large number of plant active components in human diet,which have a variety of health promoting effects.However,the absorption effect of flavonoids in vivo is very poor because of its insoluble,unstable and poor permeability.Promoting the absorption of flavonoids in vivo through oral delivery system is a hot spot in nutritional research.Our previous research found that due to the special rhamnose group,the metabolism of flavone astilbin in vivo is very unique,which is mainly absorbed and transported in the form of noumenon,and rarely forms metabolites.Therefore,we believe that astilbin is a good model flavone to compare the absorption promoting effects of different oral delivery systems in vivo.Three different oral delivery systems were constructed with zein,skimmed milk powder and cyclodextrin as carriers to compare their absorption promoting effects on astilbin in rats.The results were as follows:(1)Three shell materials,lecithin(ZNP-L),chitosan(ZNP-CH)and sodium caseinate(ZNP-SC),were used to prepared the core-shell zein nanoparticles.Astilbin was encapsulated as a model flavonoid to compared the influence of shell material on zein nanoparticles both in vitro and in vivo.The particle size was moderately increased by lecithin and sodium caseinate,but notably increased by chitosan.All the shell material provided good redispersibility for the nanoparticles and significantly improved the colloidal stability.Chitosan and sodium caseinate significantly delayed and decreased the feces excretion of astilbin in rat,while lecithin exhibited very weak effect.The results may be attributed to the difference of mucoadhesive properties between the shell materials.The results showed that the bioavailability of astilbin in rats was increased by 18.2 times,9.3 times and 1.89 times through the wrapping treatment of ZNP-CH,ZNP-SC and ZNP-L.(2)The skim milk powder loaded with astilbin was obtained by freeze drying(AST-SM-F)and spray drying(AST-SM-S).The physicochemical properties and in vivo absorption effects of the two microsomes were compared.AST-SM-S and AST-SM-F have similar encapsulation and loading efficiency(88% and 0.99%),and average particle sizes are 9.98 μm and 16.61 μm,respectively.Physical and chemical characterization showed that astilbin lost its crystal structure in both microparticles and existed in an amorphous form.The solubility and passive diffusion rate of astilbin were significantly increased by the two kinds of microparticles.Compared with AST-SM-F,AST-SM-S has better stability in simulated intestinal fluids(SIF).Both microparticles showed strong intestinal adhesion,which reduced and slowed the excretion of astilbin in rats.After oral administration,the bioavailability of astilbin in AST-SM-S group and AST-SM-F group was increased by 2.97 and 2.56 times,respectively.(3)The inclusion compounds of astilbin with β-cyclodextrin(AST-βCD),methyl-β-cyclodextrin(AST-M-βCD),2-hydroxypropyl-β-cyclodextrin(AST-2-H-βCD),sulfobutyl-β-cyclodextrin(AST-S-βCD)were prepared by cogrinding method.The stability,solubility and absorption promoting effect of four inclusion complexes were studied.The inclusion rates of the four inclusion compounds were more than 90%.The results of physicochemical tests showed that astilbin existed in amorphous form.Phase solubility method and UV absorption spectrometry showed that the cavity size of AST-M-βCD was the most suitable for the entry of astilbin,and the formed inclusion complex had the best solubility.The stability and transmembrane diffusion rate of astilbin in working intestinal gastric juice were improved by four inclusion complexes,AST-M-βCD is the most effective.Among the four inclusion complexes,only AST-βCD and AST-M-βCD reduced the excretion of astilbin.The bioavailability of astilbin in rat were 1.12,1.47,0.91 and0.71 times through AST-βCD,AST-M-βCD,AST-2-H-βCD and AST-S-βCD comparing with free astilbin,respectively.