Abstract:

With methoxy polyethylene glycol with terminal amino group (mPEG-NH₂), tetradecyl amine, 5-amino-1-pentanol, 1, 4-butanediol diacrylate and 1, 3-pentanediamine diacrylate as raw materials, the amphiphilic polymer poly (ethylene glycol)-poly (β-amino) ester (mPEG-PBAE) was synthesized by one-pot method. The structure, molecular weight and CMC of the amphiphilic polymer (mPEG-PBAE) were characterized by FT-IR, GPC and pyrene fluorescence probe. Using urushiol as the drug model molecule, the mPEG-PBAE polymer micelles loaded with urushiol were prepared by dialysis method. The particle size, Zeta potential and morphology of the micelles loaded with urushiol were characterized by TEM and DLS. The pH responsiveness, drug release and its in vitro antitumor activity were investigated. The results showed that the amphiphilic copolymer mPEG-PBAE was successfully prepared and the weight average relative molecular mass was 11 445, which was not significantly different from the designed theoretical relative molecular mass, the CMC value of the polymer was 18.25 mg/L. The entrapment efficiency was 82.29% and drug loading capacity was 23.21%, the appearance of drug loaded micelles was regular spherical structure, the size was uniform, and the average particle size was 160.1 nm. The Zeta potential value of drug loaded micelles was 33.6 mV, its particle size in the buffer solution of pH value 5.0 was significantly higher than that in solution of pH value 6.5 and 7.4, and had obvious pH responsiveness. When pH value was 5.0, the cumulative drug release rate in 72 h was 98.7%; when pH value was 6.5 and 7.4, the cumulative drug release rates in 72 h were 61.6% and 31.5%, respectively. The median inhibitory concentrations (IC₅₀) of the drug loaded micelles on HepG2 and A549 tumor cells were 1.38 and 0.87 mg/L, respectively; which showed better in vitro antitumor activity than that of free urushiol.

Key words: urushiol, pH responsiveness, amphiphilic copolymer micelle, antitumor