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ENGLISH ABSTRACT
JOURNAL ARTICLE
[The in vitro cytotoxicity and in vivo toxicity of doxorubicin antiresistant stealth liposomes].
AIM: Multidrug resistance ( MDR) as a major obstacle to successful clinical cancer chemotherapy, searching a novel effective antiresistant drug would be necessary.
METHODS: A novel doxorubicin anti-resistant stealth liposomes (DARSLs) was prepared by co-encapsulating doxorubicin (DOX) and verapamil (VER) into stealth liposomes with ammonium sulfate gradient remote loading approach. In vitro cytotoxity of various DOX formulations and in vivo toxicity of DARSLs were evaluated using DOX-resistant rat prostate cancer cell line (MLLB2), human uterus sarcoma cell line (MES-SA/DX5) and normal SD rats, separately.
RESULTS: The DARSLs liposome suspensions mainly consisted of homogeneous large unilamellar vesicles (LUV) with average particle size of (118.1 +/- 22.3) nm. Encapsulation efficiencies of DOX and VER in DARSLs were more than 90% and about 70%, respectively, when the ratio of DOX/VER/Lipid was 1: 0.11 :10 (w/w/w). In vitro cytotoxicity tests of the DARSLs using rat prostate cancer cell line (MLLB2) and human uterus sarcoma cell line (MES-SA/DX5) showed that 5 micromol x L(-1) VER significantly reversed DOX-resistance of these 2 cell lines and DARSLs was the most effective on inhibition of DOX-resistant cell growth. Besides, compared to FDFV, much slower DOX distribution (confocal microscopy) to nuclei and cytoplasm in MLLB2 cells for DARSLs suggested that it might possess distinct mechanism of cytotoxicity. Systemic and cardiac toxicity evaluations in normal SD rats suggested that liposomal encapsulation could significantly improve the severe cardiotoxicity arising from simultanous administration of DOX and VER.
CONCLUSION: DARSLs is a novel anticancer liposome formulation with lower cardiotoxicity, effective drug-resistance reversal and intravenous injection.
METHODS: A novel doxorubicin anti-resistant stealth liposomes (DARSLs) was prepared by co-encapsulating doxorubicin (DOX) and verapamil (VER) into stealth liposomes with ammonium sulfate gradient remote loading approach. In vitro cytotoxity of various DOX formulations and in vivo toxicity of DARSLs were evaluated using DOX-resistant rat prostate cancer cell line (MLLB2), human uterus sarcoma cell line (MES-SA/DX5) and normal SD rats, separately.
RESULTS: The DARSLs liposome suspensions mainly consisted of homogeneous large unilamellar vesicles (LUV) with average particle size of (118.1 +/- 22.3) nm. Encapsulation efficiencies of DOX and VER in DARSLs were more than 90% and about 70%, respectively, when the ratio of DOX/VER/Lipid was 1: 0.11 :10 (w/w/w). In vitro cytotoxicity tests of the DARSLs using rat prostate cancer cell line (MLLB2) and human uterus sarcoma cell line (MES-SA/DX5) showed that 5 micromol x L(-1) VER significantly reversed DOX-resistance of these 2 cell lines and DARSLs was the most effective on inhibition of DOX-resistant cell growth. Besides, compared to FDFV, much slower DOX distribution (confocal microscopy) to nuclei and cytoplasm in MLLB2 cells for DARSLs suggested that it might possess distinct mechanism of cytotoxicity. Systemic and cardiac toxicity evaluations in normal SD rats suggested that liposomal encapsulation could significantly improve the severe cardiotoxicity arising from simultanous administration of DOX and VER.
CONCLUSION: DARSLs is a novel anticancer liposome formulation with lower cardiotoxicity, effective drug-resistance reversal and intravenous injection.
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