Study On The Preparation Of Platinum Drug Targeting Conjugates Loaded MPEG-PGA Nanosphere

Targeting drug delivery system is the drug delivery systems by the carrier of increasing the drug concentration in the lesions of selective parts and it is a popular research field of the medical for the high bioavailability, drug side-effect and effective. In this dissertation, methoxy-poly(ethylene glycol)-poly-(L-glutamicacid)(mPEG-PGA) was used as drug carriers since its good biological biocompatibility and bio-degradability, And cisplatin loaded micelles of the amphiphilic copolymer mPEG-PGA was prepared by it through the dialysis method. In addition, bovine serum albumin (BSA) as model monoclonal antibody, mPEG-PGA-BSA conjugate was subjected to in vitro release studies. Especially, three sections of work were carried as follows:First, methoxy-polyethylene glycol amine (mPEG-NH2) was synthesized by polyethyl-ene glycol (mPEG-OH 5000) through the classic method of Gabriel. Phosgene method for 5-benzyl L-glutamate N-carboxyanhydride (L-Glu(Z)-NCA). Then through mPEG-NH2 triggered ring opening polymerization of NCA, Methoxy-polyeth-ylene glycol-poly glutamic acid benzyl ester (mPEG-PGA(Z)) was synthesized. Finally, we got mPEG-PGA by acid hydrolysis benzyl oxygen carbonyl protection of side chain. The resulting mPEG-PGA diblock copolymers were characterized by using FT-IR,’H NMR, GPC, CMC.Second, stability, particle size and morphology for blank and cisplatin loaded micelles of the amphiphilic copolymer mPEG-PGA and mPEG-PGA-BSA conjugates were investigated by DLS and TEM. From the results, it was found that the polymeric micelles had typical core-shell structure and the mean diameter was about 30 nm by TEM in a dehydrated state, the mean diameter was about 105 nm by DLS in aqueous solution and possessed good stability.Third, entrapment efficiency and drug loading of the polymer micelles and conjugates were computed by the establishment of standard curve of cisplatin through ultraviolet and visible spectrophotometer. We also considered the initial water volume, [NCA]/[PEG] ratio influence on entrapment efficiency and drug loading, found that 20% water volume(v/v), [NCA]/[PEG]=40/1, entrapment efficiency and drug loading of the polymer micelles were 57.31% and 10.35% and conjugates were 31.60% and 31.60%. In addition, in vitro release expperiments of these optimum nanospheres and conjugates were conducted at 37℃ in PBS solution with a pH value of 7.2. As a result, the micelles and conjugates showed a well controlled release behavior and sustained release about 47.68% and 42.53%.The improvement and innovation of this paper is described as follows:1、The optimized synthetic route colligated the advantages and avoided the disadvantages of the reported routes and materials can be obtained easily. Conditions and procedures are optimized.2、Based on the previous study, a novel model about a combination of targeted therapies is used, based on polymer, loaded cisplatin and coupled mAb, the conjugates Performs well about drug side-effect, effective and effect on the controlled release.