Pharmacokinetics and Antitumor Effect of Doxorubicin Carried by Stealth and Remote Loading Proliposome
Pharmacokinetics and Antitumor Effect of Doxorubicin Carried by Stealth and Remote Loading Proliposome
复制标题
隐形远程装载前脂质体阿霉素的药代动力学及抗肿瘤作用
作者：
J. P. Wang;Y. Maitani;K. Takayama;T. Nagai
目的。本研究的目的是制备携带阿霉素（DXR）的隐形远程载药前体脂质体（SRP-L），并对其药代动力学、急性毒性和抗癌作用进行评价。
方法. SRP-L为透明溶液。将SRP-L注入含DXR的0.9%NaCl水溶液中，形成脂质体并自动负载DXR（SRP-L-DXR）。采用SRP-L-DXR、心磷脂脂质体DXR（CL-DXR）和游离DXR（F-DXR）的药代动力学研究了SRP-L-DXR的长循环作用，并在C57 BL/6小鼠和小鼠子宫肌瘤M5076模型上评价了SRP-L-DXR的急性毒性和抗肿瘤作用。
结果SRP-L-DXR在纯水中的平均粒径为112.9 ± 8.6（nm），包封率在纯水中为96.5 ± 0.2%，在5%葡萄糖中为95.5 ± 0.1%，在0.9%NaCl中为98.01± 0.6%。SRP-L-DXR的血药浓度明显高于F-DXR和CL-DXR。与F-DXR相比，SRP-L-DXR的急性毒性较低，其抗癌作用依赖于治疗。
结论.研制了一种新型的前体脂质体（SRP-L），它能自动负载DXR并形成性能优良的SRP-L-DXR。SRP-L-DXR的急性毒性较低，但对M5076腹水的治疗效果并不总是优于F-DXR。
AbstractPurpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L.
Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model.
Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment.
Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
影响因子：
11.2
作者：
Ning Z. Wu;Daphne Da;Tracy L. Rudoll;David Needham;A. Whorton;M. Dewhirst
通讯作者：
Ning Z. Wu;Daphne Da;Tracy L. Rudoll;David Needham;A. Whorton;M. Dewhirst
DOI：
10.1016/0005-2736(80)90558-1
发表时间：
1980-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
SZOKA, F;OLSON, F;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
用法国压力池制成的单层脂质体：一种简单的制备和半定量技术。
影响因子：
6.5
作者：
HamiltonJr,RL;Goerke,J;Guo,LS;Williams,MC;Havel,RJ
通讯作者：
Havel,RJ