Preparation Of Hydrazone-Containing Peg-Pcl Block Copolymer Micelles For PH-Induced Drug Release

In this paper, a series of poly(ethylene glycol)-poly(ε-caprolactone) amphiphilic block copolymers with backbones containing hydrazone bonds (mPEGHydPCL, mPEGHyd(PCL)2) were designed and synthesized. Accordingly, biodegradable pH-sensitive polymeric micelles were prepared, which were studied from the particle size, morphology, critical micelle concentration (CMC), drug loading and in vitro release, etc. Three parts are included as shown as below:(1) The pH sensitive block copolymers were synthesized by a ring-opening polymerization(ROP) in the presence of hydrazone bond containing macro-initiators. The polymers were characterized and confirmed by IR,1H-NMR and gel permeation chromatography (GPC).(2) Blank and drug loaded micelles were prepared from the polymers by a co-solvent evaporation method. The transmission electron microscopy (TEM) was used to investigate the morphology of micelles, It was showed that polymeric micelles were spherical structures without aggregation.Dynamic light scattering (DLS) measurements showed that the micelles have smaller particle sizes ranging from60nm to120nm and narrow distributions. Critical micelle concentrations (CMC) of the copolymers were less than6.03×104mg/mL, which were closely related to their molecular structures and molecular weights. Drug loading content (DLC) of micelles was determined by HPLC. Paclitaxel (PTX) was loaded into these micelles and it was also found that the drug loading content greatly depended on their molecular structures and molecular weight. The in vitro drug release profiles indicated that a pH-dependental characters of the polymeric micelles containing hydrazone bonds. Drug release rates were accelerated in acidic medium compared to the medium of pH7.4.(3) In vitro cytotoxicity of blank and PTX-loaded micelle was studied by MTT assay. The blank ploymeric micelles were nearly nontoxic. In vitro cytotoxicity against A549cell lines of hydrazone-containing PTX-loaded polymeric micelles was stronger than that of PTX-loaded polymeric micelles without hydrazone bonds.