Cytotoxic Effect of Paclitaxel and Lapatinib Co-Delivered in Polylactide-co-Poly(ethylene glycol) Micelles on HER-2-Negative Breast Cancer Cells

Abstract

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 1H 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.

Rapid Self-Assembly of Polymer Nanoparticles for Synergistic Codelivery of Paclitaxel and Lapatinib via Flash NanoPrecipitation

“…The encapsulation efficiency of the drug is the amount of drug encapsulated compared to the nominal amount in the formulation. The drug loading of PTX and LAP in the single-drug-loaded nanoparticles were similar (Table 3) and comparable to previous literature using polymer micelles [27,43]. For the single-drug-loaded nanoparticles, the encapsulation efficiency PTX and the LAP were 37.6% ± 14.4% and 25.0% ± 1.5%, respectively, which are comparable to previous reports using polymer micelles [43].…”

“…The drug loading of PTX and LAP in the single-drug-loaded nanoparticles were similar (Table 3) and comparable to previous literature using polymer micelles [27,43]. For the single-drug-loaded nanoparticles, the encapsulation efficiency PTX and the LAP were 37.6% ± 14.4% and 25.0% ± 1.5%, respectively, which are comparable to previous reports using polymer micelles [43]. Interestingly, in the co-loaded nanoparticles, the encapsulation efficiency of PTX increases from 37.6% ± 14.4% to 67.0% ± 2.2% while the encapsulation efficiency for LAP in PTX-LAP NPs remained the same as the LAP NPs (Table 3).…”

“…Due to the selective increase in encapsulation efficiency of PTX in the presence of LAP, the drug loading of PTX was 2.7-fold higher than the LAP loading (2.11% ± 0.50% compared to 0.79% ± 0.49%) despite using equal amounts of each drug during mixing (0.5 mg/mL of each). Notably, these drug concentrations are comparable to previous studies micelles [27,43].…”

RepCOOL: computational drug repositioning via integrating heterogeneous biological networks

“…7, the half maximal inhibitory concentration (IC 50 ) of Tamoxifen was 32.13 µM on BT474 cells. It should be noted that the toxic effect of two drugs including, Doxorubicin and Paclitaxel has been proved on MCF-7, SKBR-3 and MCF-7 cell lines, respectively, by other researchers [27][28][29][30]. Therefore, we can consider Tamoxifen and other repurposed molecules as effective drugs for breast cancer.…”

The Therapeutic Efficacy of Dendrimer and Micelle Formulations for Breast Cancer Treatment

“…The drug-loaded micelles displayed enhanced cytotoxic effects compared to the free drugs after 48 h and 72 h on MCF-7 cell lines. The drug combination using the micelles showed synergistic effects by reducing the viability of HER-2 negative breast cancer cell lines [ 174 ]. Wu and co-workers prepared and evaluated folate targeted biodegradable polymeric MPEG- b -P(LA- co -DHC/FA) micelles loaded with paclitaxel for breast cancer cell targeting [ 175 ].…”