基于磷脂-嵌段共聚物杂化囊泡的药物载体

Drug carrier based on phospholipid-block copolymer hybrid vesicles

由聚甲基丙烯酸胆固醇酯(pCMA)-嵌段-聚甲基丙烯酸N,N-二甲氨基乙酯(pDMAEMA)共聚物(pCMA-b-pDMAEMA)和磷脂组装磷脂-嵌段共聚物杂化囊泡。通过荧光电子显微镜、动态光散射仪对磷脂嵌段共聚物杂化囊泡进行了测试。使用RAW 264.7小鼠巨噬细胞开展细胞毒性和内化实验,并考察了磷脂-嵌段共聚物杂化囊泡内药物体外释放。结果表明,1-棕榈酰-2-油酰磷脂酰胆碱(POPC)-嵌段共聚物P2〔m(pCMA)∶m(pDMAEMA)=1∶5〕杂化囊泡(POPC_(0.3)P2_(0.7),A_(3),其中0.3和0.7分别代表POPC和嵌段共聚物P2的质量,mg,下同)和POPC_(0.1)POEPC_(0.2)P2_(0.7)(A_(8),其中POEPC为1,2-二棕榈酰-sn-甘油-3-磷酰胆碱)分别与RAW 264.7小鼠巨噬细胞培养5 h后,细胞存活率分别为93.4%±1.1%和92.1%±0.8%,均高于其他样品。POPC_(0.1)POEPC_(0.2)P3_(0.7)〔P3为m(pCMA)∶m(p[DMAEMA-co-荧光素O-甲基丙烯酸酯(FIMA)])=1∶5嵌段共聚物〕比POPC_(0.3)P3_(0.7)更易被RAW 264.7小鼠巨噬细胞吸收。用磷脂-嵌段共聚物杂化囊泡A_(8)负载阿霉素(DOX)(DOX@A_(8))对人肾癌细胞OS-RC-2进行治疗,发现当DOX终浓度为3.00μmol/L时,DOX@A_(8)对人肾癌细胞OS-RC-2的抑制率为75.0%±1.1%。

Phospholipid-block copolymer hybrid vesicle was assembled from polycholesterol methacrylate(pCMA)-block-N,N-dimethylaminoethyl methacrylate copolymer(pDMAEMA)(pCMA-b-pDMAEMA)and phospholipids and characterized by fluorescent electron microscope and dynamic light scatterometer.The cytotoxicity and internalization assays were then carried out on RAW 264.7 mouse macrophages,followed by in vitro drug release analysis.The results showed that the cell survival rate of macrophages,cultured in a medium containing 1-palmitoyl-2-oleoyl phosphatidylcholine(POPC)-block-copolymer P2[m(pCMA)∶m(pDMAEMA)=1∶5]hybrid vesicles(POPC_(0.3)P2_(0.7),A_(3),where 0.3 and 0.7 represent the mass of POPC and block copolymer P2,mg,the same below)and POPC_(0.1)POEPC_(0.2)P2_(0.7)(A_(8),where POEPC is 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine phosphatidylcholine)for 5 h,was 93.4%±1.1%and 92.1%±0.8%,respectively,higher in comparison with other samples prepared.Meanwhile,POPC_(0.1)POEPC_(0.2)P3_(0.7){P3 is block copolymer with a mass ratio of pCMA to p[DMAEMA-co-fluorescein O-methacrylate(FIMA)]of 1∶5}was more easily absorbed by the RAW 264.7 mouse macrophages than POPC_(0.3)P3_(0.7).Moreover,the proliferation inhibition rate of human kidney cancer cells OS-RC-2 treated with doxorubicin(DOX)loaded in phosphipid-block copolymer hybrid vesicles A_(8)(DOX@A_(8))was 75.0%±1.1%when at a final DOX concentration of 3.00μmol/L.