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使用含阿霉素脂质体抑制艾氏腹水瘤

Ehrlich tumor inhibition using doxorubicin containing liposomes.

作者信息

Elbialy Nihal Saad, Mady Mohsen Mahmoud

机构信息

Biophysics Department, Faculty of Science, Cairo University, Giza 12613, Egypt.

Biophysics Department, Faculty of Science, Cairo University, Giza 12613, Egypt ; King Saud University, College of Science, Department of Physics and Astronomy, Riyadh 11451, Saudi Arabia.

出版信息

Saudi Pharm J. 2015 Apr;23(2):182-7. doi: 10.1016/j.jsps.2014.07.003. Epub 2014 Jul 10.

Abstract

Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.

摘要

通过皮下注射艾氏腹水癌细胞,在雌性Balb小鼠体内培育艾氏瘤。给携带艾氏瘤的小鼠注射生理盐水、溶解状态的阿霉素或由摩尔比为100:100:60:4的二肉豆蔻酰磷脂酰胆碱/胆固醇/二棕榈酰磷脂酰甘油/聚乙二醇-磷脂酰乙醇胺(DMPC/CHOL/DPPG/PEG-PE)制备的脂质体包裹的阿霉素。细胞毒性试验表明,含阿霉素的脂质体的半数抑制浓度(IC50)大于单纯阿霉素的IC50。给出了以平均肿瘤大小(cm³)表示的肿瘤生长抑制曲线。与生理盐水相比,所有阿霉素制剂均能有效抑制肿瘤生长。用载有阿霉素的脂质体治疗比单纯用阿霉素治疗对肿瘤生长的抑制作用更显著。对各组整个肿瘤切片进行组织病理学检查发现,细胞特征存在明显差异,坏死百分比也不同程度地变化,从生理盐水处理的小鼠的12%到载有阿霉素的脂质体处理的小鼠的70%。所提出的脂质体制剂可通过内吞作用(或被动扩散)将药物有效递送至肿瘤细胞,并使肿瘤细胞内阿霉素浓度升高。研究表明,脂质体阿霉素制剂提高了阿霉素的治疗指数,并增强了对艾氏瘤模型的抗肿瘤活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb81/4420998/f9de394398c2/gr1.jpg

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