Tamoxifen embedded in lipid bilayer improves the oncotarget of liposomal daunorubicin in vivo
Tamoxifen embedded in lipid bilayer improves the oncotarget of liposomal daunorubicin in vivo
复制标题
DOI：
10.1039/c3tb21423k
复制
发表时间：
2014-01-01
影响因子：
7
通讯作者：
Peng, H. S.
中科院分区：
文献类型：
--
作者：
Li, M. H.;Yu, H.;Peng, H. S.
本研究的目的是通过静脉注射研究脂质体柔红霉素加他莫昔芬在乳腺癌小鼠模型中的血浆药代动力学和生物分布。使用 HPLC 测定药代动力学研究中柔红霉素和他莫昔芬的血浆水平。使用体内成像评估了负载花青染料 (cy7) 的各种载体的生物分布。给药后，游离柔红霉素和他莫昔芬按照两室动力学模型迅速从血液中清除。柔红霉素的清除率和AUC（0-无穷大）为（平均值+/- SD）：0.028 +/- 0.005 L h(-1) kg(-1)和367.489 +/- 56.979 mu g mL(-1) h(-1)（脂质体），以及2.235 +/- 0.347 L h(-1) kg(-1)和4.546 +/- 0.704 mu g mL(-1) h(-1)（游离药物）。注射后24小时离体成像，肿瘤区域cy7+他莫昔芬脂质体的荧光强度明显高于游离cy7脂质体。总之，他莫昔芬可以改善脂质体柔红霉素的药代动力学特征，增强对乳腺癌的治疗。
The objective of this research is to investigate the plasma pharmacokinetics and bio-distribution of liposomal daunorubicin plus tamoxifen in breast cancer murine models through intravenous administration. Daunorubicin and tamoxifen plasma levels in pharmacokinetics studies were determined using HPLC. Biodistributions of various carriers loaded with a cyanine dye (cy7) were evaluated using in vivo imaging. After administration, free daunorubicin and tamoxifen were rapidly cleared out from the blood following a two-compartment kinetic model. The clearances and AUC (0-infinity) of daunorubicin were (means +/- SD): 0.028 +/- 0.005 L h(-1) kg(-1) and 367.489 +/- 56.979 mu g mL(-1) h(-1) (liposomes), and 2.235 +/- 0.347 L h(-1) kg(-1) and 4.546 +/- 0.704 mu g mL(-1) h(-1) (free drug). By ex vivo imaging 24 h after injection, the fluorescence intensity of liposomal cy7 plus tamoxifen in tumor region was obviously higher than that of free liposomal cy7. In conclusion, tamoxifen can improve pharmacokinetics profile of liposomal daunorubicin with enhanced therapy for breast cancer.