Study On Apigenin Lipid Nanocapsules

Apignin (apigenin, AP) is a natural flavonoid, which is known to have a variety of biological activities and pharmacological actions such as anti-tumor effect, chemotherapy sensitivity, protection of the tissue, organ and system, influence on the reproductive endocrine function, endocrine regulation, low toxicity, non-teratogenie and mutagenic effects, protection of radiation damage, regulation of differentiation and antibacterial, antiviral and antioxidant activity. However, AP is water-insoluble and has low solubility in high hydrophilic or non-polar solvents, thus its oral bioavailability is very low. In order to improve oral absorption, Apigenin-lipid nanocapsule (AP-LNC) was prepared in this paper. The physicochemical properties and the absorption site in rat model were studied to determine the possibility of LNC as an oral administration carrier for AP.AP-LNC was prepared with phase inversion method and the formulation was optimized by simplex lattice experiment design with drug loading as the index. The optimal formulation was as follows:20mg AP,30mg lecithin,35mg NaCl, the total amount of oil phase, surfactant and water is1.97g,40%(w/w) polyethylene glycol monostearate (surface active agent),25%(w/w) chain triglyceride (oil phase),35%(w/w) distilled water (aqueous phase). The preparation process of AP-LNCs is simple with high reproducibility and higher entrapment efficiency, the drug concentration in AP-LNC system was5.88mg/ml, that is to say, the drug’s dispersion or solubility in water was significantly improved. The shape of AP-LNCs was spherical under transmission electron microscope with good dispersion and stability with no adhesion, the polydispersity index was0.271. The average particle size was46.1nm and ζ-potential was-28.18mV. The in vitro release behavior of the AP-LNC was investigated with dialysis method, the results showed that LNC could control the release of AP.The absorption of AP-LNC at the gastrointestinal tract was studied using in situ perfusion method in rats. The intestinal absorption kinetics of AP-LNC with low. middle, high concentration were investigated and the Ka values were0.0831h-1、0.0853h-1and0.0860h-1, respectively. So the principal absorption mechanism of AP-LNC in intestine followed passive diffusion. The test of main absorption segment indicated that AP from LNC could be absorbed by all the segments of intestine, and the absorption percentages in duodenum, jejunum, ileum and colonic were (43.93±8.53)%,(40.98±1.86)%.(44.67±2.70)%and (42.54±4.94)%, respectively.