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.
Conclusion: 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.