Research On Insulin Release From Insulin-loaded Liposomal Nanohybrid Cerasomes

Diabetes has become the third refractory disease risk for human health. Insulinis the mainstay of drug therapy for patients with insulin-dependent diabetes mellitus.However, there are several limitations to the delivery of free insulin, such as poorstability in vivo，poor permeability, lack of lipophilicity, short half-life as a result ofthe inactivation and digestion by various proteolytic enzymes. The clinical use ofinsulin injection and administration for all life bring great suffering andinconvenience for patients. Therefore，the delivery of insulin by nonparenteralroutes and controlled release system has been studied by more and morepharmaceutisis over the world.Oral administration of insulin is a perfect way to improve patients’ complianceand achieve frequent administration of the therapeutic. An ideal delivery system fororal administration of insulin should protect insulin from influence of theenvironment of the gastrointestinal tract, prolong its intestinal residence time,increase the permeability of the mucosal epithelium to increase their absorption inthe small intestine and provide the intact drug to the systemic circulation.In this paper, insulin-loaded ployvvinylpyrrolidon (PVP)-doped andchitosan-coated cerasomes (PCCs) were prepared via thin-film rehydration methodand layer-by-layer (LBL). The main results were as follows:1)The size distributionand zeta potential of the PCCs were analyzed by90Plus/BI-MAS dynamic lightscattering analyzer. The results confirmed the formation of Si-O-Si network on thesurface of the cerasomes and the chitosan successfully deposited on the surface ofthe cerasomes.2)The morphology of insulin-loaded PCCs was examined bytransmission electron microscope (TEM) and sanning electron microsope (SEM).The results indicated that the PCCs were spherical and the vesicular size thatmeasured by TEM and SEM was consistent with that evaluated using DLS.3)Theencapsulation efficiency and drug loading content were examined by a UV-visspectrophotometer. The experiments showed that the PCCs successfully entrappedinsulin with encapsulation efficiency of82.03±7.53%and durg loading content of0.62±0.057(g/g).4)The dialysis method was used in vitro release experiments. Theresults indicated that both inuslin-loaded cerasomes and insulin-loaded PCCs hadslow-release effect.and significantly good controlled release effect conpared withthe release curve of free insulin or insulin-loaded conventional liposomes.5)Theresults of in vivo hypoglycemic effect experiments indicated that the insulin-loadedPCCS significantly improved glucose toerance from0hours to even10-12hoursafter oral administration. These findings indicated that such nanoparticles can be a promising approachfor the construction of an effective controlled release delivery system of insulin aswell as other proteins with short half-life time.