Co-administration of paclitaxel and cisplatin liposomal improves efficacy and reduces toxicity of chemotherapy agents in murine breast cancer model
DOI:
https://doi.org/10.1590/s2175-97902026e24211Palavras-chave:
Synergism, cytotoxicity, Antitumor efficacy, Toxicity, Combined therapyResumo
Paclitaxel (PTX) and cisplatin (CDDP) are potent cytotoxic drugs that target distinct intracellular pathways employed together for breast cancer therapy. While studies indicate enhanced treatment efficacy with drug combinations, the concomitant rise in adverse effects remains a concern. This study assessed the potential of co-administration of these drugs encapsulated into pH-sensitive liposomes (SpHL) against a murine triple-negative breast cancer model. The cytotoxicity studies revealed a concentration-dependent relationship between drug concentration and cell viability for both drugs. The combination effect of free drugs at IC50 and IC50 x2 showed an additive effect, while co-treatment with SpHL-PTX:SpHL-CDDP at IC50 x4 (1:3 molar ratio) displayed strong synergism (CI = 0.52). Other combinations exhibited antagonism (CI > 2.0). In vivo studies were performed at PTX:CDDP 1:3 molar ratio in two regimen protocols: single or dual dose protocol, resulting in different cumulative doses. Tumor growth was significantly decreased when two doses of free or encapsulated drugs were used compared to single-dose administration. Notably, encapsulated dual-dose treatments demonstrated enhanced antitumor efficacy, diminished systemic toxicity, and zero mortality. In conclusion, our study underscores the promising potential of co-administering encapsulated drugs into SpHL, highlighting their superior efficacy and reduced toxicity in breast cancer treatment compared to free drugs.
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