Study Of Synthesis、Characters And Drug Delivery About A Novel Acid-labile Amphiphilic Copolymers

A new type of amphiphilic block copolymers, polyethylene glycol-poly (2-methyl-acrylicacid2-methoxy-5-methyl-[1,3]dioxin-5-ylmethyl ester), PEG-b-PMME, bearing acid-labilesix-membered ortho ester rings in side chains was synthesized by reversible-additionfragmentation chain transfer polymerization (RAFT). The block copolymers can be self-assembled into micelles in aqueous solution. The characterization of block copolymers wasstudied by1HNMR, GPC and TGA.The fluorescence spectroscopy using Nile Red as the fluorescent probe was applied todetermine the critical micelle concentration (CMC) of block copolymers. The CMC of PEG-b-PMME20，PEG-b-PMME40and PEG-b-PMME60was estimated to be1.0×10-3,4.1×10-4and1.0×10-4g/L. The PEG-b-PMME micelles were stable in aqueous buffer at physiological pHwith a low critical micelle concentration. Particle size distributions were investigated bydynamic light scattering (DLS). We found that the average micelle diameter of PEG-b-PMME20,PEG-b-PMME40and PEG-b-PMME60increased with longer PMME block, and calculated to be150,180and230nm respectively with a narrow polydispersity of less than0.3.Nile Red as a model drug was encapsulated into the micelles to explore the release profiles.The Nile Red-loaded polymeric micelles showed rapid release of Nile Red in weakly acidicenvironments (pH=5) but slow release under physiological condition (pH=7.4), due to differenthydrolysis rate of ortho ester side-chains of PEG-b-PMME. The Paclitaxel (PTX)-loadedmicelles retained potency in killing liver cancer cells (A549), compared with the free PTX.No obvious toxicity was found in vitro and in vivo after intraperitoneal injection of themicelles, which confirmed that the PEG-b-PMME micelles with unique acid-labilecharacteristic have great potential as nano-scaled carriers for drug delivery.All of the above results stated that the amphiphilic block copolymer micelles exhibitedbetter profiles as drug carriers, which indicated that the PEG-b-PMME micelles have greatpotential to be used as nano-scales drug delivery carriers.