Cytotoxic Effect of Paclitaxel and Lapatinib Co-Delivered in Polylactide-co-Poly(ethylene glycol) Micelles on HER-2-Negative Breast Cancer Cells
Résumé
To find better strategies to enhance the cytotoxic effect of paclitaxel (PTX) and lapatinib (LAP) against breast cancer cells, we analyzed the efficacy of a novel delivery system containing polylactide-co-poly(ethylene glycol) (PLA-PEG) filomicelles of over 100 nm in length and spherical micelles of approximately 20 nm in diameter. The 1 H NMR measurements confirmed the incorporation of PTX and LAP into micelles. Analysis of the drug release mechanism revealed the diffusion-controlled release of LAP and anomalous transport of PTX. Drug content analysis in lyophilized micelles and micellar solution showed their good storage stability for at least 6 weeks. Blank micelles, LAP-loaded micelles and free LAP did not affect MCF-7 breast cancer cell proliferation, suggesting that the cytotoxicity of PTX-, PTX/LAP-loaded micelles, and the binary mixture of free PTX and LAP was solely caused by PTX. PTX/LAP-loaded micelles showed greater toxicity compared to the binary mixture of PTX and LAP after 48 h and 72 h. Only free PTX alone induced P-gp activity. This study showed the feasibility of using a LAP and PTX combination to overcome MDR in MCF-7 cells, particularly when co-loaded into micelles. We suggest that PTX/LAP micelles can be applicable not only for the therapy of HER-2-positive, but also HER-2-negative breast cancers.
Domaines
Chimie
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