Abstract
Drug carriers are composed of polymeric micelle have great therapeutic potential. One problem need to be solved is how to make this kind of carriers have long-circulation and controlled-release ability. In order to reduce critical micelle concentration (CMC) to lift in vivo stability of drug carriers, and bring the enhanced permeability and retention effect to full play, a novel comb-like amphiphilic copolymer which is composed of γ-poly (glutamic acid)-graft-poly lactide (γ-PGLA) synthesized in this study successfully. In this research, we used carbodiimide-based reaction to graft aromatic-end poly lactide onto the protonated γ-poly-(glutamic acid). The micellar solution prepared by a pseudo-solvent-evaporation method, and the particle size of polymeric micelle was between 110nm~150nm with narrow distribution. Additionally, we found that the smallest micelle was formed when hydrophilic/hydrophobic ratio equals to 1/2. The spherical structure of micelle was identified by AFM and SEM images. For convenient storage and micellar stability, we used glucose instead of poly vinyl alcohol which has slight toxicity as the lyoprotectant to lyophilize and preserve the micelle. From fluorescence spectra, we found that the CMC would reduced with higher hydrophobic ratio of copolymers. Furthermore, γ-PGLA copolymers have lower CMCs than conventional block-copolymers in each hydrophilic/hydrophobic ratio； this result indicated that the comb-like copolymers can be expected to form more stable micelle. Paclitaxel-encapsulation results revealed that drug/polymer ratio can be considerably raised if we removed organic solvents by rotary evaporator rapidly. The result of in-vitro release study indicated the faster releasing rate in higher paclitaxel-loading micelle, this may result from that encapsulated paclitaxel will interfere with core stability of micelle. Finally, the in-vitro cytoxicity test demonstrated that this new material can be a non-toxic and efficient carrier for paclitaxel, and the paclitaxel-loading micelle was more sensitive to inhibit hela cells than 3T3 cells. Keywords: graft-copolymer, comb-like, amphiphilic, drug carrier, CMC, in-vitro release, cytoxicity