高级检索

聚乙二醇单甲醚-聚乳酸-聚谷氨酸/聚赖氨酸的合成及其复合胶束的稳定性研究

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

  • 摘要: 制备等比例的聚乙二醇单甲醚-聚乳酸-聚谷氨酸(mPEG-PLA-PLG)和聚乙二醇单甲醚-聚乳酸-聚赖氨酸(mPEG-PLA-PLL)电中性聚离子复合胶束,依靠静电吸引提高原聚合物胶束聚乙二醇单甲醚-聚乳酸(mPEG-PLA)的结构稳定性。在mPEG-PLA的羟基末端引入氨基,分别与谷氨酸和赖氨酸的环化羧酸酐(NCA)发生开环反应,并且脱保护基制得目标产物,通过1H NMR、IR确证其结构,荧光法比较载体改性前后的临界胶束浓度(CMC)。以透析法制备去氧鬼臼毒素聚合物胶束,HPLC法测定改性前后两种胶束的载药量和包封率,激光粒度仪和HPLC比较两种胶束25 ℃水浴过程中粒径和药物含量的变化。两者的CMC都较低,且载药量和包封率相近,但改性后胶束的稳定性增至原胶束的2倍以上,稳定性得到显著提高。

     

    Abstract: 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.

     

/

返回文章
返回