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  • Title: Developing combination of artesunate with paclitaxel loaded into poly-d,l-lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response.
    Author: Tran BN, Nguyen HT, Kim JO, Yong CS, Nguyen CN.
    Journal: Drug Dev Ind Pharm; 2017 Dec; 43(12):1952-1962. PubMed ID: 28724314.
    Abstract:
    OBJECTIVES: Paclitaxel (PTX) has been indicated for the treatment of a variety of solid tumors, whereas artesunate (ART) has been reported to have the potential for use in combination chemotherapy. In this study, the combination of ART and PTX was prepared in nanoparticle to induce the synergic effect and improve therapeutic efficiency in treatment of breast cancer. METHODS: Dual anticancer agents (PTX and ART) were loaded into Poly-D,L-lactic-co-glycolic acid (PLGA) nanoparticle (NP) by solvent evaporation technique from oil-in-water emulsion, stabilized with Tween 80. Physicochemical properties of obtained nanoparticles (PTX-ART-NPs) were characterized including particle size (Z), polydispersity index (PDI), zeta potentials (ZP), encapsulation efficiency (EE), and in-vitro drug release. Combination index (CI) was calculated to determine the synergic effect of the combination and select the best ratio of ART and PTX. The final NPs analyzed intracellular uptake, cytotoxicity assay, and apoptosis study. RESULTS: The final NP had a small size (around 120 nm) with a narrow size distribution (PDI <0.3). EE values for each drug were 87.8 ± 1.1% and 99.5 ± 0.1% for ART and PTX, respectively, and drugs were released from NPs in a controlled release pattern. All combinations of PTX and ART had CI values under 1, which confirmed the synergic effects. Meanwhile, NP preparation increased cytotoxicity on three breast cancer cell-lines comparable to free drugs. CONCLUSIONS: Combination of ART- and PTX-loaded PLGA NP showed promising results for anticancer therapy, especially for breast cancer treatment.
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