title: The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient.
abstract: The applications of ethylenediaminetetraacetic acid (EDTA) have been expanded from the treatment of heavy metal poisoning to chelation therapies for atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and mortality by chelating toxic metal ions. In this study, EDTA was used in a drug delivery system by adopting an NH4EDTA gradient method to load doxorubicin into liposomes with the goal of increasing therapeutic effects and decreasing drug-related cytotoxicity. The particle size of the optimum NH4EDTA gradient liposomes was 79.4±1.87 nm, and the entrapment efficiency was 95.54%±0.59%. In vitro studies revealed that liposomes prepared using an NH4EDTA gradient possessed long-term stability and delayed drug release. The in vivo studies also showed the superiority of the new doxorubicin formulation. Compared with an equivalent drug dose (5 mg/kg) prepared by (NH4)2SO4 gradient, NH4EDTA gradient liposomes showed no significant differences in tumor inhibition ratio, but cardiotoxicity and liposome-related immune organ damage were lower, and no drug-related deaths were observed. These results show that use of the NH4EDTA gradient method to load doxorubicin into liposomes could significantly reduce drug toxicity without influencing antitumor activity.
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Jiangsu Hansoh Pharmaceutical Co., Ltd., Lianyungang, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Qingjing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: She
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Livzon Mabpharm Inc., Zhuhai, People's Republic of China.
authors.forename: Eliza
authors.initials: E
authors.lastname: Lu
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004492:Edetic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D006321:Heart / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D009374:Neoplasms, Experimental / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D012995:Solubility; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D004492:Edetic Acid
keywords: NH4EDTA; antitumor activity; doxorubicin; ion gradient; liposome; toxicity