Submit Manuscript  

Article Details


Development of Long-Circulating and Fusogenic Liposomes Coencapsulating Paclitaxel and Doxorubicin in Synergistic Ratio for the Treatment of Breast Cancer

[ Vol. 16 , Issue. 9 ]

Author(s):

Marjorie Coimbra Roque, Marina Santiago Franco, José Mário Carneiro Vilela, Margareth Spangler Andrade, André Luís Branco de Barros, Elaine Amaral Leite and Mônica Cristina Oliveira*   Pages 829 - 838 ( 10 )

Abstract:


Background: The co-encapsulation of paclitaxel (PTX) and doxorubicin (DXR) in liposomes has the potential to offer pharmacokinetic and pharmacodynamic advantages, providing delivery of both drugs to the tumor at the ratio required for synergism.

Objective: To prepare and characterize long-circulating and fusogenic liposomes co-encapsulating PTX and DXR in the 1:10 molar ratio (LCFL-PTX/DXR).

Methods: LCFL-PTX/DXR was prepared by the lipid film formation method. The release of PTX and DXR from liposomes was performed using a dialysis method. Studies of cytotoxicity, synergism, and cellular uptake were also carried out.

Results: The encapsulation percentage of PTX and DXR was 74.1 ± 1.8 % and 89.6 ± 12.3%, respectively, and the mean diameter of the liposomes was 244.4 ± 28.1 nm. The vesicles remained stable for 30 days after their preparation. The drugs were simultaneously released from vesicles during 36 hours, maintaining the drugs combination in the previously established ratio. Cytotoxicity studies using 4T1 breast cancer cells showed lower inhibitory concentration 50% (IC50) value for LCFL-PTX/DXR treatment (0.27 ± 0.11 μm) compared to the values of free drugs treatment. In addition, the combination index (CI) assessed for treatment with LCFL-PTX/DXR was equal to 0.11 ± 0.04, showing strong synergism between the drugs. Cell uptake studies have confirmed that the molar ratio between PTX and DXR is maintained when the drugs are administered in liposomes.

Conclusion: It was possible to obtain LCFL-PTX/DXR suitable for intravenous administration, capable of releasing the drugs in a fixed synergistic molar ratio in the tumor region.

Keywords:

Breast cancer, liposomes, co-encapsulation, paclitaxel, doxorubicin, synergism, cell uptake.

Affiliation:

Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Center for Innovation and Technology, SENAI-FIEMG, Campus CETEC, Belo Horizonte, Minas Gerais, Center for Innovation and Technology, SENAI-FIEMG, Campus CETEC, Belo Horizonte, Minas Gerais, Department of Clinical and Toxicological Analyzes, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais



Read Full-Text article