THERAPY OF PRIMARY AND METASTATIC MOUSE MAMMARY CARCINOMAS WITH DOXORUBICIN ENCAPSULATED IN LONG CIRCULATING LIPOSOMES
THERAPY OF PRIMARY AND METASTATIC MOUSE MAMMARY CARCINOMAS WITH DOXORUBICIN ENCAPSULATED IN LONG CIRCULATING LIPOSOMES
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DOI：
10.1002/ijc.2910510618
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发表时间：
1992-07-30
影响因子：
6.4
通讯作者：
MARTIN, F
中科院分区：
文献类型：
--
作者：
VAAGE, J;MAYHEW, E;MARTIN, F
本研究的目的是比较阿霉素在3种不同制剂中的治疗效果：（1）PBS，（2）由卵磷脂酰甘油/卵磷脂酰胆碱/胆固醇/dl-α-生育酚组成的常规脂质体，和（3）由氢化大豆磷脂酰胆碱/胆固醇/聚乙二醇-二硬脂酰磷脂酰乙醇胺组成的空间稳定的长循环“隐形”脂质体。多柔比星制剂用于治疗最近植入的和良好建立的生长中的原发性小鼠乳腺癌，并抑制乳房内肿瘤植入物自发转移的发展。在最近植入的原发性肿瘤的治疗中，从肿瘤植入后3或10天开始，在15天内以3次静脉内注射给予制剂。在良好建立的原发性肿瘤的治疗中，小鼠在22天内接受4次静脉注射，平均在肿瘤植入后38天开始。在针对转移的预防性治疗中，在原发性肿瘤植入后22天或58天开始，在22天内以4次静脉内注射给予制剂。Stealth脂质体制剂在降低肿瘤MC 19和肿瘤MC 65乳房内植入物转移的发生率、治愈近期植入肿瘤MC 2A、肿瘤MC 2B和肿瘤MC 65的小鼠以及增加已明确植入肿瘤MC 2B的小鼠的8周存活率方面，比常规脂质体制剂或游离药物显著更有效。可以得出结论，隐形脂质体阿霉素制剂的长循环时间是其上级治疗效果的原因。
The purpose of our study was to compare the therapeutic effects of doxorubicin in 3 different formulations: (1) in PBS, (2) in conventional liposomes composed of egg phosphatidylglycerol/egg phosphatidylcholine/cholesterol/dl-alpha-tocopherol, and (3) in sterically stabilized, long-circulating "Stealth" liposomes composed of hydrogenated soy phosphatidylcholine/cholesterol/polyethylene glycol-distearoylphosphatidylethanolamine. The doxorubicin formulations were used to treat recently implanted and well-established, growing primary mouse mammary carcinomas, and to inhibit the development of spontaneous metastases from intra-mammary tumor implants. In the treatment of recently implanted primary tumors, the formulations were given in 3 i.v. injections over 15 days, starting 3 or 10 days after tumor implantation. In the treatment of well-established primary tumors, the mice received 4 i.v. injections over 22 days, starting an average 38 days after tumor implantation. In the preventive treatment against metastases, the formulations were given in 4 i.v. injections over 22 days, starting 22 days or 58 days after primary tumor implantation. The Stealth liposome formulation was significantly more effective than the conventional liposome formulation or the free drug in reducing the incidence of metastases from intra-mammary implants of tumor MC19 and tumor MC65, in curing mice with recent implants of tumor MC2A, tumor MC2B, and tumor MC65, and in increasing the 8-week survival of mice with well-established implants of tumor MC2B. It is concluded that the long circulation time of the Stealth liposome doxorubicin formulation accounts for its superior therapeutic effectiveness.