Liposomes Containing Gadodiamide: Preparation, Physicochemical Characterization, and In Vitro Cytotoxic Evaluation.
BACKGROUND
The aim of this study was to develop, characterize and assess the cytotoxic activity of pHsensitive (pHL-Gd), stealth pH-sensitive (SpHL-Gd), and conventional (convL-Gd) liposomes containing gadodiamide (Gd-DTPA-BMA).


METHODS
Formulations were prepared by reverse-phase evaporation method and their physicochemical properties were evaluated by means of particle size, zeta potential, and Gd-DTPA-BMA entrapment. SpHL-Gd was considered being the most promising liposome, since it combines stealth and fusogenic characteristics that might contribute to achieve higher therapeutic efficiency. Their drug encapsulation percentages have been optimized satisfactorily. The addition of Gd-DTPA-BMA at 125 μmol/mL in the SpHL-Gd preparation allowed obtaining liposomes with appropriate encapsulation percentage (20.3 ± 0.1%) and entrapment (25.4 ± 0.1 μmol/mL).


RESULTS
The cytotoxic studies on the 4T1 breast cancer cell line demonstrated that liposomes-loaded with Gd-DTPA-BMA inhibited cancer cell. pHL-Gd and SpHL-Gd liposomes showed higher activity than convL-Gd and free Gd-DTPA-BMA, indicating that the pH-sensitive characteristic was important to improve intracellular delivery.


CONCLUSIONS
The presence of polyethylene glycol (PEG) in the SpHL-Gd formulation did not affect the pH-sensitivity and internalization. Therefore, the results of this study suggest the feasibility of liposomes containing Gd-DTPA-BMA as a new promising controlled delivery system.
Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Ana Luiza Chaves
ALC
Maia
Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Christian
C
Fernandes
Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Cynthia Nara Pereira
CNP
de Oliveira
Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Claudia Salviano
CS
Teixeira
Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Mariana Silva
MS
Oliveira
Federal University of Itajubá, Rua Irmã Ivone Drumond, 200, Distrito Industrial II, 35903-087, Itabira, Minas Gerais, Brazil.
Daniel Cristian Ferreira
DCF
Soares
Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Gilson Andrade
GA
Ramaldes
D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D019786:Gadolinium DTPA / Q000737:chemistry*; D006801:Humans; D008081:Liposomes; D010316:Particle Size; D011092:Polyethylene Glycols
D008081:Liposomes; D011092:Polyethylene Glycols; C064925:gadodiamide; D019786:Gadolinium DTPA
4T1 breast cancer cell line; Antineoplastic agent; Gd-DTPA-BMA; cancer treatment; in vitro cytotoxic evaluation; liposomes