title: Membrane-Loaded Doxorubicin Liposomes Based on Ion-Pairing Technology with High Drug Loading and pH-Responsive Property.
abstract: In order to achieve high drug loading and high entrapment efficiency, a doxorubicin-cholesteryl hemisuccinate ion-pair complex (DCHIP) was formed, and the ion-pair complex liposomes (DCHIP-Lip) were prepared based on conventional thin-film dispersion method. Firstly, DCHIP was fabricated and confirmed with FTIR,1H-NMR, DSC, and XRD techniques. Afterwards, DCHIP-Lip were prepared and evaluated in terms of particle size, zeta potential, entrapment efficiency, and drug loading content. Finally, the in vitro and in vivo behavior of liposomes was further investigated. The DCHIP-Lip had a nanoscale particle size of about 120 nm with a negative zeta potential of about -22 mV. In addition, the entrapment efficiency and drug loading content of DOX reached 6.4 ± 0.05 and 99.29 ± 0.3%, respectively. Importantly, the release of DCHIP-Lip was pH sensitive and increased cell toxicity against MCF-7 cells was achieved. Upon dilution, the liposomes were fairly stable under physiological conditions. The in vivo pharmacokinetic study indicated that the AUC of DOX in DCHIP-Lip was 11.48-fold higher than that of DOX-HCl solution and the in vivo antitumor activity of DCHIP-Lip showed less body weight loss and a significant prohibition effect of tumor growth. Based on these findings, it can be seen that the ion-pairing technology combined with conventional liposome drug loading method could be used to achieve high drug loading and it could be valuable for the study of liposomal delivery system.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: University of Alberta, 116 St. and 85 Ave, Edmonton, Alberta, Canada.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Yinrong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Kan
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China. bbpharmcaibb@sina.com.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D002788:Cholesterol Esters / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells / Q000187:drug effects / Q000502:physiology; D008561:Membrane Fusion / Q000187:drug effects; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D002788:Cholesterol Esters; D004338:Drug Combinations; D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; C013440:cholesteryl succinate
keywords: cholesteryl hemisuccinate; doxorubicin liposomes; in vitro release; in vivo study; ion-pair complex