title: Cytarabine-AOT catanionic vesicle-loaded biodegradable thermosensitive hydrogel as an efficient cytarabine delivery system.
abstract: Carrier with high drug loading content is one of the most important issues in drug delivery system. In the present work, an ion-pair amphiphilic molecule composed of anticancer drug cation and surfactant anion is used for straightforward fabricating vesicles for cancer therapy. Anticancer drug (cytarabine hydrochloride) and anionic surfactant (AOT) are selected for the fabrication of ion-pair amphiphilic molecule. One amphiphilic molecule contains one drug cation, thus the drug loading content is 50% (mol/mol) in theory. The in vitro drug release study shows that the release time of cytarabine is about 3 times of the pure cytarabine solution and the permeability of cytarabine has been improved about 160 times tested by parallel artificial membrane permeability assay model. However, the hemolytic toxicity is largely decreased in the studied concentration range. The in vitro cytotoxicity results show that cytarabine-AOT amphiphiles have a much lower IC50 (drug concentration resulting in 50% cell death) value and a higher cell inhibition rate comparing with their respective components, indicating its effective therapy for leukemic cells. To obtain a longer and a convenient drug release system, the prepared vesicles are further incorporated into the thermosensitive PLGA-PEG-PLGA hydrogel to prepare a subcutaneous administration. The in vivo drug release results indicate that cytarabine-AOT vesicle-loaded hydrogel is a good injectable delivery system for controlled release of cytarabine for cancer therapy.
authors: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China.
authors: Jing
authors: J
authors: Liu
authors: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China; School of Chinese Medicine, The Chinese University of Hongkong, Shatin, N.T., Hong Kong, PR China.
authors: Yue
authors: Y
authors: Jiang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, P.O. Box 29, No. 103 Wenhua Road, Shenhe District, Shenyang, Liaoning Province, PR China.
authors: Yuting
authors: Y
authors: Cui
authors: School of Chinese Medicine, The Chinese University of Hongkong, Shatin, N.T., Hong Kong, PR China.
authors: Chuanshan
authors: C
authors: Xu
authors: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China.
authors: Xiaoqing
authors: X
authors: Ji
authors: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China. Electronic address: yuxialuan@sdu.edu.cn.
authors: Yuxia
authors: Y
authors: Luan
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004143:Dioctyl Sulfosuccinic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D004912:Erythrocytes / Q000187:drug effects; D018922:HL-60 Cells; D006461:Hemolysis / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D020100:Hydrogels; D020014:K562 Cells; D008567:Membranes, Artificial; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011817:Rabbits; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D008567:Membranes, Artificial; D013501:Surface-Active Agents; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D003561:Cytarabine; D004143:Dioctyl Sulfosuccinic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols
keywords: Catanionic vesicle; Cytarabine-AOT amphiphile; Sustained drug release; Thermosensitive hydrogel