| Autor: |
Marjorie Coimbra Roque, Caroline Dohanik da Silva, Marthin Raboch Lempek, Geovanni Dantas Cassali, André Luís Branco de Barros, Marília Martins Melo, Mônica Cristina Oliveira |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Biomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112307- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
0753-3322 |
| DOI: |
10.1016/j.biopha.2021.112307 |
| Popis: |
Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid tumors to this combination, a synergism of cardiotoxicity may limit the use. Thus, the objective of this work was to investigate the toxicity of long-circulating and fusogenic liposomes co-encapsulating PTX and DXR at the synergistic molar ratio (1:10) (LCFL-PTX/DXR). For this, clinical chemistry, histopathological analysis and electrocardiographic exams were performed on female Balb/c mice that received a single intravenous dose of LCFL-PTX/DXR. The results of the study indicated that the LD50 dose range (lethal dose for 50% of animals) of the LCFL-PTX/DXR treatment (28.9–34.7 mg/kg) is much higher than that found for free PTX/DXR treatment (20.8–23.1 mg/kg). In addition, liposomes promoted cardiac protection by not raising CK-MB levels in animals, keeping cardiomyocytes without injury or electrocardiographic changes. After 14 days of treatment, free PTX/DXR caused prolongation of the QRS interval when compared to LCFL-PTX/DXR treatment at the same dose (37.0 ± 5.01 ms and 30.83 ± 2.62 ms, respectively, with p = 0.017). The survival rate of animals treated with LCFL-PTX/DXR was three times higher than that of those treated with free drugs. Thus, it was established that the toxicity of LCFL-PTX/DXR is reduced compared to the combination of free PTX/DXR and this platform has advantages for the clinical treatment of breast cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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