Insulin Loaded Nanoparticles Prepared From PELGE Triblock Copolymers As A Potential Intravascular Drug Delivery System

Biodegradable copolymeric nanoparticle drug delivery system is potentially applicable in the controlled drug release and drug targeted delivery. However, to realize the intravascular delivery of polypeptide and protein drugs using biodegradable copolymeric nanoparticle drug delivery system, it is required to overcome the rapid clearance of reticuloendothelial system (RES) and to increase the time circulation in vivo of drug loaded nanoparticles. In this project, we chose the triblock copolymer of mPEG-PLGA-mPEG (PELGE) which was synthesized with monomethoxypolyethylene glycol (mPEG) to modify poly(lactic acid-co-glycolic acid) (PLGA) as the biodegradable copolymeric device in order to increase the hydrophilic nature of the polymer, to overcome the rapid clearance of RES and to increase the time circulation of the nanoparticles. Insulin was chosen as the model polypeptide and protein drug because it is one of the most well known therapeutic proteins and it has become the standard treatment for diabetes. We studied a series of PELGE triblock copolymeric nanoparticles (INS-PELGE-NPs), in which the following researches are included: the preparation, physical and chemical properties, freeze-drying technique, in vitro drug release, in vivo pharmacologic effect, and cytotoxicity. The potential application in the triblock copolymer based polypeptide and protein drug preparations for intravascular drug delivery system has also been discussed.Through investigations of column efficiency, separation efficiency and symmetry factor, a rapid and effective chromatographic procedure for the determination of insulin entrapment efficiency in triblock copolymeric nanoparticles using RP-HPLC was developed. Method evaluations have been conducted and results indicated that the method had high sensitivity and fine reproducibility, which also achieved high selectivity and separation for the determination of entrapment efficiency of INS-PELGE-NPs. The acidic degradation product (A21-DI), alkaline degradation product (B3-DI), various...