Study On Folic Acid Conjugated Polymeric Materials As Oral Insulin Carriers

In the research of drug delivery,choosing effective drugs and appropriate carriers is an important method in order to delivery drugs more effectively and reduce side effects.Most of the recent literatures concentrate on the novel drug delivery systems made of biodegradable polymeric nanoparticles,which are promising materials in the therapy of diabetics,cancer and cardiovascular diseases.Polymeric vesicles self-assembled from amphiphilic polymers are capable of encapsulating both hydrophilic and hydrophobic drugs due to their hydrophilic shell and hydrophobic core in aqueous solutions.They are easy to be synthesized and modified,and they are more stable than liposomes due to their low critical micellar concentration(CMC).Besides,it was found that the modifications of folic acid could facilitate the targeting delivery of nanoparticles,or enhance the oral absorption efficiency of nanocarriers.In this paper,novel folated Pluronic F127/poly(lactic-co-glycolic)block copolymers(FA-F127-PLGA and FA-P85-PLGA)were synthesized.According to the morphology of the nanoparticles determined by transmission electron microscope,we chose FA-P85-PLGA vesicles as carriers for oral insulin delivery,while FA-F127-PLGA micelles were used for targeted paclitaxel(PTX)delivery.FA-P85-PLGA vesicles were used as oral insulin carriers in this paper.The particle size of insulin-loaded FA-P85-PLGA vesicles was 119.1 nm.In vitro studies of insulin-loaded FA-P85-PLGA vesicles showed that encapsulating insulin into FA-P85-PLGA vesicles can protect insulin from degration by enzyme,and also obtain a long-lasting release behavior in vitro.Moreover,oral administration of insulin-loaded FA-P85-PLGA vesicles to diabetic rats could achieve a significant and long-lasting hypoglycemic effect.6h after oral administration,the plasma glucose level of diabetic rats administrated at an insulin dose of 100IU/kg decreased to 13.4% of initial level,and this hypoglycemic effect lasted for another 6h.Comparing with subcutaneous injection of insulin,oral insulin-loaded FA-P85-PLGA vesicles could achieve a mild but more efficient decrease of plasma glucose,which means FA-P85-PLGA vesicles are promising in the research of oral insulin delivery system.In vitro release study on FA-F127-PLGA micelles showed that FA-F127-PLGA were capable of prolonging the release of PTX,thus increase the treatment time.MTT assays showed that folate-targeted FA-F127-PLGA nanoparticles were more effective than nontargeted PLGA-F127-PLGA nanoparticles when delivering PTX into folate receptor over expressing OVCAR-3 cells.According to the pharmacokinetics study,FA-F127-PLGA nanoparticles were capable of prolonging the treatment time of PTX and delaying the elimination of PTX in plasma.Therefore FA-F127-PLGA nanoparticles could be used as targeting carriers for hydrophobic drugs such as PTX.