title: Thermo-Sensitive Liposome co-Loaded of Vincristine and Doxorubicin Based on Their Similar Physicochemical Properties had Synergism on Tumor Treatment.
abstract: To develop vincristine (VCR) and doxorubicin (DOX) co-encapsulated thermo-sensitive liposomes (VD-TSL) against drug resistance, with increased tumor inhibition rate and decreased system toxicity, improving drug targeting efficiency upon mild hyperthermia (HT) in solid tumor.
  
  
  
  Based on similar physicochemical properties, VCR and DOX were co-loaded in TSL with pH gradient active loading method and characterized. The time-dependent drug release profiles at 37 and 42°C were assessed by HPLC. Then we analysed the phospholipids in filtrate after ultrafiltration and studied VD-TSL stability in mimic in vivo conditions and long-time storage conditions (4°C and -20°C). Cytotoxic effect was studied on PANC and sw-620 using MTT. Intracellular drug delivery was studied by confocal microscopy on HT-1080. In vivo imaging of TSL pharmacokinetic and biodistribution was performed on MCF-7 tumor-bearing nude mice. And therapeutic efficacy on these xenograft models were followed under HT.
  
  
  
  VD-TSL had excellent particle distribution (about 90 nm), high entrapment efficiency (>95%), obvious thermo-sensitive property, and good stability. MTT proved VD-TSL had strongest cell lethality compared with other formulations. Confocal microscopy demonstrated specific accumulation of drugs in tumor cells. In vivo imaging proved the targeting efficiency of TSL under hyperthermia. Then therapeutic efficacy revealed synergism of VCR and DOX co-loaded in TSL, together with HT.
  
  
  
  VD-TSL could increase drug efficacy and decrease system toxicity, by making good use of synergism of VCR and DOX, as well as high targeting efficiency of TSL.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Pharmacy Department, No. 261 Hospital of PLA, Beijing, 100094, People's Republic of China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, People's Republic of China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Institute of Transfusion Medicine, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Song
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, People's Republic of China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China. ddsnano@126.com.|, No.27 Taiping Road, Haidian District, Beijing, China. ddsnano@126.com.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Mei
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China. usnitro2004@126.com.|, No.27 Taiping Road, Haidian District, Beijing, China. usnitro2004@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy; D055598:Chemical Phenomena / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008081:Liposomes; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D013696:Temperature; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D014750:Vincristine / Q000008:administration & dosage* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D014750:Vincristine; D004317:Doxorubicin
keywords: doxorubicin; hyperthermia; solid tumor; thermo-sensitive liposome; vincristine