Preparation And Characterization Of Biodegradable PEG And Its Conjugate Loading With Camptothecin

Camptothecin has high anti-cancer activity, but its clinical use was limited because of poor water solubility and high toxic side effects. PEG-neutral, low toxicity, with unique physical and chemical properties and good biocompatibility, is one of medical polymers approved by FDA. The use of PEG as a drug carrier, often with a solubility enhanced, half-life prolonged, maximum plasma concentration decreased, enzymatic degradation lessen, immunogenicity and antigenicity of decreased, is one of the most effective methods to solve the problems of clinical application of camptothecin. In order to solve the problem of rapid renal clearance of small molecular weight PEG or renal cumulative toxicity of large molecular weight PEG simultaneously, this paper studies the synthesis of large molecular weight biodegradable PEG and its conjugate loading with CPT.FTIR, HPLC, ~1H-NMR analysis showed that ultra-high molecular weight poly (succinate-PEG) ester was obtained by the ring-opening polymerization and the gradual condensation polymerization of PEG with molecular weight less than 20,000 and succinic anhydride. The polymerization reaction of PEG and succinic acid assisted with microwave is a typical esterification condensation reaction. Its reaction condition is mild (80 ~ 90℃) and the molecular weight of poly (succinate-PEG) ester can be controlled. The use of microwave can accelerated the esterification polymerization rate significantly. The reaction time reduced from the traditional esterification polymerization of 36h to 30 ~ 45min.The result of degradation experiments in vitro showed that poly (succinate-PEG) ester is biodegradable.The conjugate of the ultra-high molecular weight biodegradable poly (succinate-PEG) ester loading CPT were prepared through solvent method, which can form a solid dispersion and assemble to nanoparticles in the aqueous solution. Drug-loading rate of CPT nanoparticles are close to theoretical value when molar ratio of PEG ester and CPT is no more than 1:30. Results of in vitro release experiments showed that the CPT nanoparticles had significant slow-release and controlled release properties.The CPT prodrug using biodegradable macromolecular polymer PEG as the carrier is prepared by microwave-assisted method and two kinds of conventional synthetic route methods.Results of FTIR, HPLC, ~1H-NMR showed that the target product were obtained. At the same time, succinate-PEG ester loading with CPT has a certain sustained-release effect, and the cumulative release rate declined while the amount of drug increased. The hydrolysis is the key to affect the drug release.