医用生物相容性接枝共聚物负载阿霉素和香豆素的研究

Studies on Loading Doxorubicin and Coumarin by Medical Biocompatible Graft Copolymer

以一端连有单电子转移自由基聚合(RAFT)链转移剂的聚乙二醇(PEG)为大分子链转移剂,调控2-(4-羟基丁酰氧基)甲基丙烯酸叔丁酯(t BHBMA)的RAFT聚合,得到的PEG-b-Pt BHBMA嵌段共聚物引发丙交酯的开环聚合,制得接枝共聚物PEG-b-(Pt BA-g-PLA).通过聚乳酸末端的羟基与7-甲氧基香豆素-3-羧酸(COU)中羧基的酯化反应,得到了含有荧光标记分子的接枝共聚物PEG-b-(Pt BA-g-PLA-COU).该聚合物主链选择性水解,得到了含有荧光标记分子的两亲性接枝共聚物PEG-b-(PAA-g-PLA-COU).以PEG-b-(PAA-g-PLA-COU)为药物载体,对阿霉素(DOX)进行了负载,制得了含有荧光标记分子的聚合物载药胶束.利用紫外光谱和动态光散射测定了载药胶束的载药量和胶束尺寸.

The end of linear m-PEG-OH was functionalized to provide m-PEG-CTA macro-RAFT agent. RAFT homopoly- merization of tBHBMA was conducted to give PEG-b-PtBHBMA diblock copolymer, which initiated ROP of lactide directly. The obtained graft copolymer, PEG-b-（PtBA-g-PLA）, was then esterified with 7-methoxycoumarin-3- carboxylic acid to af- ford PEG-b-（PtBA-g-PLA-COU） containing fluorescent dye molecule. PEG-b-（PAA-g-PLA-COU） amphiphilic graft copolymer was prepared by selective hydrolysis of PtBA segment. Finally, doxorubicin （DOX） was loaded into polymeric micelles aggregated by PEG-b-（PAA-g-PLA-COU）. The drug loading content （DLC） and size of the obtained polymeric drug micelles containing fluorescent dye molecule was measured by UV-vis and DLS.