title: pH-Sensitive, Long-Circulating Liposomes as an Alternative Tool to Deliver Doxorubicin into Tumors: a Feasibility Animal Study.
abstract: Therapeutic agents used in chemotherapy have low specificity leading to undesired severe side effects. Hence, the development of drug delivery systems that improve drug specificity, such as liposome moieties, is an alternative to overcome chemotherapy limitations and increase antitumor efficacy. In this study, the biodistribution profile evaluation of pH-sensitive long-circulating liposomes (SpHL) containing [99mTc]DOX in 4T1 tumor-bearing BALB/c mice is described.
  
  
  
  [99mTc]DOX was radiolabeled by direct method. Liposomes were prepared and characterized. [99mTc]DOX was encapsulated into liposomes by freezing and thawing. Circulation time for SpHL-[99mTc]DOX was determined by measuring the blood activity from healthy animals. Biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 24 h after injection.
  
  
  
  Blood levels of the SpHL-[99mTc]DOX declined in a biphasic manner, with an α half-life of 14.1 min and β half-life of 129.0 min. High uptake was achieved in the liver and spleen, due to the macrophages captured. Moreover, tumor uptake was higher than control tissue, resulting in high tumor-to-muscle ratios, indicating higher specificity for the tumor area.
  
  
  
  [99mTc]DOX was successfully encapsulated in liposomes. Biodistribution indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. In summary, these results showed the higher accumulation of SpHL-[99mTc]DOX in the tumor area, suggesting selective delivery of doxorubicin into tumor.
authors.affiliation: Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Juliana O
authors.initials: JO
authors.lastname: Silva
authors.affiliation: Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Renata S
authors.initials: RS
authors.lastname: Fernandes
authors.affiliation: Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sávia C A
authors.initials: SC
authors.lastname: Lopes
authors.affiliation: Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Valbert N
authors.initials: VN
authors.lastname: Cardoso
authors.affiliation: Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Leite
authors.affiliation: Biological Science Institute, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Geovanni D
authors.initials: GD
authors.lastname: Cassali
authors.affiliation: Department of Radiology, Molecular Imaging, Interventional Radiology, NeuroRadiology, Medical Physics, Pathology, Biomarkers Unit, Clinical Laboratory, Microbiology Unit, Rovigo & Adria Hospital, Rovigo, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marzola
authors.affiliation: Department of Radiology, Molecular Imaging, Interventional Radiology, NeuroRadiology, Medical Physics, Pathology, Biomarkers Unit, Clinical Laboratory, Microbiology Unit, Rovigo & Adria Hospital, Rovigo, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.affiliation: Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Monica C
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. brancodebarros@yahoo.com.br.
authors.forename: Andre Luis Branco
authors.initials: AL
authors.lastname: de Barros
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000473:pathology; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D013667:Technetium; D004317:Doxorubicin
keywords: 4T1 murine model; Cancer; Doxorubicin; Long circulating; Tumor; pH-sensitive liposome