Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: the lack of beneficial effects by coating liposomes with poly(ethylene glycol).
Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: the lack of beneficial effects by coating liposomes with poly(ethylene glycol).
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小鼠Lewis肺癌中脂质体脂质和封装的阿霉素的积累：用聚乙二醇包被脂质体缺乏有益效果。
DOI：
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发表时间：
1997
影响因子：
3.5
通讯作者：
Marcel B. Bally
中科院分区：
文献类型：
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作者：
Michael J. Parr;D. Masin;Pieter R. Cullis;Marcel B. Bally
在静脉内施用包封在二硬脂酰磷脂酰胆碱/胆固醇脂质体中的多柔比星后，测量肿瘤中药物蓄积的效率，所述脂质体在存在或不存在5摩尔%聚乙二醇修饰的磷脂酰乙醇胺（PEG-PE）的情况下制备。这些阿霉素脂质体制剂以最大耐受剂量给予皮下建立的刘易斯肺癌雌性BDF-1小鼠。用于确定肿瘤靶向效率（T（e））的参数包括多柔比星血浆（AUC（P））和肿瘤（AUC（T））浓度-时间曲线下面积。评价给药后7天内血浆和肿瘤中脂质和药物水平的延长时程研究表明，不含PEG-PE的脂质体的T（e）（AUC（T）/AUC（P））更大。游离阿霉素、二硬脂酰磷脂酰胆碱/胆固醇脂质体包封阿霉素和二硬脂酰磷脂酰胆碱/胆固醇/PEG-PE稳定脂质体包封阿霉素给药后的AUC（P）分别为0.087 μ mol x ml（-1）x h、50 μ mol x ml（-1）x h和78 μ mol x ml（-1）x h。两种脂质体多柔比星制剂在肿瘤中达到的最大药物水平相似，为140 μ g（250 nmol）/g肿瘤;然而，当脂质体不含PEG-PE时，达到该水平更快。游离药物给药后测得的最大水平小于5微克/克肿瘤，这些都是在15分钟内实现的。结果表明，与使用PEG修饰的脂质体，如增加血液中的水平和提高循环寿命的一些好处，可能是最大限度地提高脂质体药物在肿瘤生长部位的积累方面的优势不大。
The efficiency of drug accumulation in tumors was measured after intravenous administration of doxorubicin encapsulated in distearoyl phosphatidylcholine/cholesterol liposomes prepared in the presence or absence of 5 mol % polyethylene glycol-modified phosphatidylethanolamine (PEG-PE). These liposomal formulations of doxorubicin were administered at the maximum tolerated dose in female BDF-1 mice bearing subcutaneously established Lewis Lung carcinoma. The parameters used to determine tumor targeting efficiency (T(e)) included area under the doxorubicin plasma (AUC(P)) and tumor (AUC(T)) concentration-time curves. Extended time-course studies evaluating lipid and drug levels in plasma and tumors during 7 days after administration indicated that the T(e) (AUC(T)/AUC(P)) was greater for liposomes that did not contain PEG-PE. The AUC(P) after administration of free doxorubicin, doxorubicin encapsulated in distearoyl phosphatidylcholine/cholesterol liposomes and doxorubicin encapsulated in distearoyl phosphatidylcholine/cholesterol/PEG-PE-stabilized liposomes were 0.087 micromol x ml(-1) x h, 50 micromol x ml(-1) x h and 78 micromol x ml(-1) x h, respectively. Maximum drug levels achieved in the tumors were similar for both liposomal doxorubicin formulations, 140 microg (250 nmol)/g tumor; however, this level was achieved faster when the liposomes did not contain PEG-PE. Maximum levels measured after administration of free drug were less than 5 microg/g tumor, and these were achieved within 15 min. The results suggest that some of the benefits associated with the use of PEG-modified liposomes, such as increased blood levels and enhanced circulation lifetime, may be of little advantage in terms of maximizing liposomal drug accumulation in sites of tumor growth.
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