Novel Drug Delivery System Based on Docetaxel-Loaded Nanocapsules as a Therapeutic Strategy Against Breast Cancer Cells

Paola Sánchez-Moreno,José Manuel Peula-García,Houria Boulaiz,Juan Luis Ortega-Vinuesa,Antonia Aránega

doi:10.3390/ijms13044906

Paola Sánchez-Moreno, José Manuel Peula-García + Show 3 more

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https://doi.org/10.3390/ijms13044906

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Abstract

In the field of cancer therapy, lipid nanocapsules based on a core-shell structure are promising vehicles for the delivery of hydrophobic drugs such as docetaxel. The main aim of this work was to evaluate whether docetaxel-loaded lipid nanocapsules improved the anti-tumor effect of free docetaxel in breast cancer cells. Three docetaxel-loaded lipid nanocapsules were synthesized by solvent displacement method. Cytotoxic assays were evaluated in breast carcinoma (MCF-7) cells treated by the sulforhodamine B colorimetric method. Cell cycle was studied by flow cytometry and Annexin V-FITC, and apoptosis was evaluated by using propidium iodide assays. The anti-proliferative effect of docetaxel appeared much earlier when the drug was encapsulated in lipid nanoparticles than when it was free. Docetaxel-loaded lipid nanocapsules significantly enhanced the decrease in IC50 rate, and the treated cells evidenced apoptosis and a premature progression of the cell cycle from G(1) to G(2)-M phase. The chemotherapeutic effect of free docetaxel on breast cancer cells is improved by its encapsulation in lipid nanocapsules. This approach has the potential to overcome some major limitations of conventional chemotherapy and may be a promising strategy for future applications in breast cancer therapy.

Highlights

Breast cancer is the most common malignant tumor and the first cause of morbidity and mortality among women worldwide [1,2]
We found a greater reduction in inhibitory concentration 50 (IC50) rate when the docetaxel was encapsulated in lipid nanoparticles, with evidence of apoptosis and premature cell cycle progression from G(1) to G(2)-M phase
Chitosan is a polysaccharide obtained from the deacetylation of chitin, which is a structural element of the exoskeleton of crustaceans

Summary

Introduction

Breast cancer is the most common malignant tumor and the first cause of morbidity and mortality among women worldwide [1,2]. Adjuvant chemotherapy with taxanes reduces the risk of cancer recurrence and death in patients with early or operable breast cancer and has shown benefits in patients with high-risk node-negative breast cancer. These novel chemotherapeutics have led to improvements in survival, they are associated with numerous drug-related toxicities [6]. Docetaxel has been associated with a significant increase in neutropenia, febrile neutropenia, leucopenia, stomatitis, edema, fatigue and/or asthenia, and diarrhea [6] These effects are due in part to the high doses used to achieve the desired anti-tumor effect, which are necessary because of the non-specific distribution of both novel and traditional chemotherapies, with only a small fraction of drugs reaching the tumor. The drugs can accumulate in healthy organs, and there is a fine line between tolerability and severe morbidity, e.g., in the case of doxorubicin, a DNA intercalator that produces cardiotoxicity [8]

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