Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio - 13/11/21
pages | 9 |
Iconographies | 6 |
Vidéos | 0 |
Autres | 0 |
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | LCFL-PTX/DXR reduced in vivo toxicity compared to free PTX/DXR. |
• | ECG showed that LCFL-PTX/DXR induced lower cardiac toxicity compared to free PTX/DXR. |
• | Survival of animals treated with LCFL-PTX/DXR is three times higher than free PTX/DXR. |
• | The dose of LCFL-PTX/DXR tolerated by mice is 27% higher than that of free drugs. |
Keywords : Liposomes, Doxorubicin, Paclitaxel, Co-administration, Acute toxicity, Breast cancer
Plan
Vol 144
Article 112307- décembre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?