Synthesis And Drug Release Of Poly(Ethylene Glycol)-Block-Polyalanine

Many antineoplastic agents such as curcumin and doxorubicin are hardly soluble in water,which greatly limits their use in clinical treatment.Polymeric micelle is a novel drug carrier that can be used for targeted and insoluble therapeutic agents.The micelles have hydrophobic cores and hydrophilic shells that are aggregated into a spherical or other structure of nano-sized particles by self-assembly of amphiphilic macromolecules or surfactants in solution.Compared with the micelles formed by the usual surfactants,the polymeric micelles are more stable and can dissolve a large amount of hydrophobic compounds in their nuclei.Due to the hydrophilic shell and the nano-sized diameter,the polymeric micelles have prolonged residence time in the tumor tissue and have a passive targeting to the tumor tissue.Therefore,the design and preparation of different structures of polymer micelles,and exploration the controlled release and the targeting rules of antitumor drug becomes one of research hot spots of biomedical field.This paper is divided into the following parts:First,the polymer micelles and the formation mechanism,preparation method,drug loading process and release process of polymer micelles are briefly introduced.Second,L-alanine N-carboxyanhydride and D-alanine N-carboxyanhydride monomers were synthesized by L/D-alanine and triphosgene as raw materials.Poly(ethylene glycol)-bpolyalanine(PEG-b-PA)between poly(L/D-alanine)and poly(ethylene glycol)(PEG)was successfully prepared by NCAs and amino polyethylene glycol monomethyl ether(MPEGNH2).The prepared NCA monomers and PEG-b-PAs were characterized by IR,NMR and gel permeation chromatography.Third,the polymeric micelles based on PEG-b-PA were prepared by dialysis,and their morphology was observed by transmission electron microscopy(TEM).The PEG-b-PA micelles showed spherical structure and uniform size,and their size was about 20 nm.The effects of different p H,dialysis time,amount of block copolymer and drug dosage on the drug loading and release of PEG-b-PA micelles were determined by UV-Vis spectrophotometer(UV).The results showed that the release of curcumin was changed from burst to sustained release when the ratio of L-alanine units to D-alanine units was 1: 0.25,the ratio of monomer to initiator was 70: 1,and 72 h of dialysis.