Ehrlich tumor inhibition using doxorubicin containing liposomes

被引:29
作者
Elbialy, Nihal Saad [1 ]
Mady, Mohsen Mahmoud [1 ,2 ]
机构
[1] Cairo Univ, Fac Sci, Dept Biophys, Giza 12613, Egypt
[2] King Saud Univ, Coll Sci, Dept Phys & Astron, Riyadh 11451, Saudi Arabia
关键词
Liposomes; Doxorubicin; Ehrlich carcinoma; Cytotoxicity; PEG; DPPG; VASCULAR-PERMEABILITY; SOLID TUMOR; PHARMACOKINETICS; TOXICITY; COLLAGEN;
D O I
10.1016/j.jsps.2014.07.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 2014 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.
引用
收藏
页码:182 / 187
页数:6
相关论文
共 27 条
[1]   LIPOSOMES CONTAINING SYNTHETIC LIPID DERIVATIVES OF POLY(ETHYLENE GLYCOL) SHOW PROLONGED CIRCULATION HALF-LIVES INVIVO [J].
ALLEN, TM ;
HANSEN, C ;
MARTIN, F ;
REDEMANN, C ;
YAUYOUNG, A .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1066 (01) :29-36
[2]   Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo [J].
Barraud, L ;
Merle, P ;
Soma, E ;
Lefrançois, L ;
Guerret, S ;
Chevallier, M ;
Dubernet, C ;
Couvreur, P ;
Trépo, C ;
Vitvitski, L .
JOURNAL OF HEPATOLOGY, 2005, 42 (05) :736-743
[3]   P-glycoprotein: The intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer [J].
Chung, HC ;
Rha, SY ;
Kim, JH ;
Roh, JK ;
Min, JS ;
Lee, KS ;
Kim, BS ;
Lee, KB .
BREAST CANCER RESEARCH AND TREATMENT, 1997, 42 (01) :65-72
[4]   Toxicity of doxorubicin entrapped within long-circulating liposomes [J].
Daemen, T ;
Regts, J ;
Meesters, M ;
TenKate, MT ;
BakkerWoudenberg, IAJM ;
Scherphof, GL .
JOURNAL OF CONTROLLED RELEASE, 1997, 44 (01) :1-9
[5]   Low Power Argon Laser-Induced Thermal Therapy for Subcutaneous Ehrlich Carcinoma in Mice Using Spherical Gold Nanoparticles [J].
Elbialy, Nihal ;
Abdelhamid, Mahmoud ;
Youssef, Tareq .
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 2010, 6 (06) :687-693
[6]   Pharmacokinetics of pegylated liposomal doxorubicin - Review of animal and human studies [J].
Gabizon, A ;
Shmeeda, H ;
Barenholz, Y .
CLINICAL PHARMACOKINETICS, 2003, 42 (05) :419-436
[7]   A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics Adriamycin and daunorubicin [J].
Gewirtz, DA .
BIOCHEMICAL PHARMACOLOGY, 1999, 57 (07) :727-741
[8]   Interaction of type-I collagen with phospholipid monolayer [J].
Ghannam, MM ;
Mady, MM ;
Khalil, WA .
BIOPHYSICAL CHEMISTRY, 1999, 80 (01) :31-40
[9]   Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice [J].
Ishida, O ;
Maruyama, K ;
Sasaki, K ;
Iwatsuru, M .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1999, 190 (01) :49-56
[10]   Exploiting the enhanced permeability and retention effect for tumor targeting [J].
Iyer, Arun K. ;
Khaled, Greish ;
Fang, Jun ;
Maeda, Hiroshi .
DRUG DISCOVERY TODAY, 2006, 11 (17-18) :812-818