Preparation and stability of poly(ethylene glycol)monomethyl ether-poly(D, L-lactic acid)-poly(glutamic acid)/poly lysine triblock complex micelle

In order to improve the structural stability of the original polymeric micelles based on poly(ethylene glycol)monomethyl ether-poly(D, L-lactic acid)(mPEG-PLA)copolymer conjugate, the electroneutral polyion complex micelles with equal proportion of poly(ethylene glycol)monomethyl ether-poly(D, L-lactic acid)-poly(glutamic acid)(mPEG-PLA-PLG)and poly(ethylene glycol)monomethyl ether-poly(D, L-lactic acid)-poly lysine(mPEG-PLA-PLL)were prepared. The enhanced stability of the new micelle was attributed to electrostatic attraction. The target products were obtained by reacting the amino boded terminal hydroxyl group of mPEG-PLA with cyclic carboxylic acid anhydridesof glutamic acid and lysine, respectively through ring opening reaction, and subsequent protecting group removal. Their structures were identified by ¹H NMR and IR, and the differences of the critical micelle concentration(CMC)between mPEG-PLA and the modified polymers were measured by fluorescence. Dialysis was empolyed to prepare deoxypodophyllotoxin loaded polymeric micelles. The drug-loading capacity and encapsulation efficiency of mPEG-PLA micelles and electroneutral polyion complex micelle were determined by HPLC. The change of their particle size and drug content in 25 °C water bath were assessed by laser particle analyzer(dynamic light scattering)and HPLC, respectively. Both micelles had low CMC value and similar drug-loading capacity and encapsulation efficiency. However, the stability of the polymer complex micelles was two times higher than that of mPEG-PLA, which represented a significant enhancement.