Abstract
Polymeric micelles as drug carriers have drawn much attention in recent decades, because amphiphilic copolymers can self-assemble to form micelles in water due to hydrophilic and hydrophobic interactions. In this study, poly(ethylene glycol) methyl ether and poly aromatic anhydride were used to act as hydrophilic and hydrophobic group, respectively. Four different polymers (mPEG5000CPP、mPEG5000CPH、mPEG2000CPP、mPEG2000CPH) were synthesized using melt condensation approach. The physical and chemical properties of polymer were evaluated by 1H-NMR、FT-IR and GPC. Through critical micelle concentration (CMC) and surface chemical structure analysis, we confirmed that micelles can be formed in very low concentration and had a stable hydrophobic core. The micelles sizes were measured smaller than 200 nm and had good stability during 30 days degradation test. The four different polymeric micelles showed low cytotoxicity toward human fibroblast cells by MTT assay. With curative effect in cancer, hydrophobic drugs, paclitaxel and curcumin, which are difficult to dissolve in PBS (with solubility of 1.17×10-6 and 2.99×10-8 mole/L, respectively) are of interests. We can improve the solubility of paclitaxel fourty-fold and curcumin five thousand-fold by micelles encapsulation. Paclitaxel were incorporated into these micelles with encapsulation efficiency around 55% to 75%, depending on the different loading ratio and with drug content around 3.56%. High loading efficiency around 75% as well as drug content around 6.83% were observed in curcumin-loaded micelles. In both paclitaxel and curcumin micielles there were no initial burst phenomenon observed. Both micelles showed sustained release for about 18 days, with curcumin released faster than paclitaxel. According to the size of drug-loaded micelles，the stability of drug-loaded micelles，encapsulation efficiency and drug release curve, paclitaxel-loaded in mPEG5000CPP（D/P＝0.050）and curcumin-loaded in mPEG5000CPP（D/P＝0.075）are shown to be the best formulation for each drug we tested. Paclitaxel- and curcumin-loaded micelles showed IC50 values of about 6.27 and 4.66 ppm of the drugs, respectively, toward HeLa cell. This means that drugs are effective toward cancer cells and can kill cancer cells in very low concentrations. As a result, we conclude that nano-micelles of methoxy poly(ethylene glycol-b-aromatic anhydride) may be suitable for encapsulating those hydrophobic anti-cancer drugs.