Study On Insulin Phytosome And Self-microemulsion

Currently, multiple daily injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, frequent injections lead to poor compliance which is associated drawbacks with this treatment. Oral administration of insulin may be beneficial to such patients as it is easy to take and with higher treatment compliance, but orally administered insulin is encountered with many difficulties such as rapid degradation and poor intestinal absorption which are the key factors constraining the development of oral insulin formulations on market..The conformation study by CD (Circular Dichroism):A CD method was utilized to study the conformation of insulin in various formulation composition and technological conditions, including the organic solvent, temperature, pH value, and also the carrier materials, emusifer and co-emulsifier, so that providing basis and reference for optimizing the preparation conditions of particulate.Phytosome study A reasonable criterion of accurate evaluation was established by which such factors as time, the ratio of baicalein to lecithin and the concentration of reactant was examined,then the phytosome was prepared by orthogonal experimental design with 5% acetic acid in methanol as solvent. Various methods were used to explore The physicochemical properties of the phytosome were studied by IR,XRD and CD, and the results suggested the formation of phytosome with non-covalent reduced the aggregation of the molecule.Compared with insulin,the solubility of phytosome in water, n-octanol and MCT was effectively enhanced, and moreover the bioactivity didn't change.Study of insulin self-microemulsion based on phytosome The phytosome was dissolved in proper oil, the solubility study and ternary phase diagram method were used to choose emusifer and co-emulsifier, the final composition of self-microemulsion formulation was MCT:Cremphor RH40:Transcutol P(20:40:40),3.62mg/g insulin could be loaded, and when met with water, it formed O/W ball microemulsion below 50nm instantaneously, the self-emulsifying efficiency and particle size were not affected by pH value and volume of dilution. And compared with insulin solution, the stability of phytosome and self-microemulsion based on phytosme in artificial gastric juice with pepsin and artificial intestinal juice with trypsin was improved significantly.The empty self-microemulsion was orally administered to mice for 14 days, no significant difference in body weight between empty self-microemulsion and water fed, and no apparent change in micro structure of stomach and intestinal by scanning electron microscopy.Evaluation on safty and pharmacodynamics of insulin self-microemulsion The empty self-microemulsion was orally administered to mice for 14 days, no significant difference in body weight between empty self-microemulsion and water fed, and no apparent change in microstructure of stomach and intestinal by scanning electron microscopy. Compared with insulin solution, phytosome and self-microemulsion administred orally both could decreased the blood glucose of STZ-induced diabetic rat apprantely, and self-microemulsion was much better than phytosome dissolved in oil with absolute bioavailability of 4.59%. Moreover, hypoglycemic effect of self-microemulsion administered orally was sustained for a longer time compared to subcutaneous injection.The result indicated the self-microemulsifying delivery system base on the phytosome was expected to become good carrier for oral delivery of insulin.