Pluronic P85Vesicles As Novel Carriers For Oral Insulin Delivery

For the injection drugs like insulin, the patient suffers enormously from the repeated injections, which makes it urgency to study oral insulin carriers. Oral insulin carriers are able to load the insulin, which could protect insuin from the enzymatic degradation in the gastrointestinal (GI) tract. Insulin can then be transported effectively into the blood circultaiton and thus the blood glucose concentration can be decreased. Polymeric vesicles are composed of the hydrophobic bilayer and the hydrophilic core, which makes it possible to protect the insulin through loading the insulin into the hydrophilic core.In this thesis, poly(lactic acid)-polyethylene glycol-poly(lactic acid)(PLA-PEO-PLA) block copolymers containing two kinds of PLA block lengths were synthesized by our group. The assembling behaviors between the triblock copolymer PLA-PEO-PLA and the pentablock copolymer PLA-Pluronic F127-PLA (PLA-PEO-PPO-PEO-PLA) were compared. The morphologies of PLA-F127-PLA nanoparticles are vesicles and those of PLA-PEO-PLA nanoparticles are spherical micelles. It was concluded that the PPO block in Pluronic F127decreased the Gibbs free energy on the interface of vesicles to help the formation of PLA-F127-PLA vesicles. Therefore, another pentablock copolymer PLA-Pluronic P85-PLA was synthesized. The PLA-P85-PLA nanoparticles were proved to be vesicles from the TEM picture and their mean diameter is131.6nm from light scattering results.Both in vitro and in vivo release behaviors of insulin loaded in PLA-P85-PLA vesicles were studied. It was observed that insulin was released out gradually from PLA-P85-PLA vesicles and almost all insulin was released out7.5h later. More importantly, for the oral administration of insulin-loaded PLA-P85-PLA vesicles at insulin doses of200IU/kg, the minimum blood glucose concentration was observed in the diabetic mice test after2.5h, which was15%of initial glucose level. Furthermore, the blood glucose concentration increased slowly to31.8%of initial blood glucose concentration after10.5h and was maintained at this level for at least an additional14h (32.5%of initial blood glucose concentration at24.5h). These results proved that PLA-P85-PLA vesicles could be promising polymeric carriers for oral insulin delivery application due to their sustained and enhanced hypoglycemic effect.Polymeric vesicles can not only load the hydrophilic drugs but also load the hydrophobic drugs. Therefore, the hydrophobic drug paclitaxel was also loaded in PLA-P85-PLA vesicles and their in vitro release behaviors were studied. It was indicated that paclitaxel loaded in PLA-P85-PLA vesicles was released out only12%in4days. However, the paclitaxel entrapped in PLA-P85-PLA vesicles was able to kill more cancer cells than the free paclitaxel.