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Uptake and Cytotoxicity of Docetaxel-Loaded Hyaluronic Acid-Grafted Oily Core Nanocapsules in MDA-MB 231 Cancer Cells

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ABSTRACT

Purpose

It is hypothesized that docetaxel (Doc)-loaded hyaluronic acid (HA)-polyethylene glycol/poly(ε-caprolactone)-grafted oily core nanocapsules (NCs) can enhance the drug cytotoxicity and uptake in CD44 expressing breast cancer (BC) cells (MDA-MB 231).

Methods

NCs were prepared, optimized and characterized by dynamic light scattering, transmission electron microscopy (TEM), and powder X-ray diffraction (PXRD). In vitro cytotoxicity tests [MTS, level of reactive oxygen species (ROS) and level of reduced glutathione (GSH)] were performed in BC cells. The contribution of CD44 to the NCs cellular uptake was elucidated using an anti CD44 antibody blockage and a CD44 negative NIH3T3 cell line.

Results

The optimum formulation of Doc-loaded HA oily core NCs had respective mean diameter, polydispersity, and drug encapsulation efficiency of 224.18 nm, 0.32, and 60.38%. The NCs appeared spherical with low drug crystallinity, while the drug release data fitted to first order equation. Compared to that of ungrafted NCs, the cytotoxicity of Doc-loaded HA-grafted NCs was significantly enhanced (p<0.05). A decrease of the intracellular level of ROS was reversely correlated with that of GSH. Interestingly, the cellular internalization of HA-grafted NCs mediated CD44 was dramatically enhanced (3 to 4-fold) with respect to the absence of specific biomarker or targeting ligand.

Conclusions

The use of HA-grafted NCs enhanced the selective drug payload, cytotoxicity and uptake in MDA-MB 231 cells. Therefore, it could be a promising template for safe and effective delivery of Doc and similar chemotherapeutic agents in cancer cells.

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ACKNOWLEDGMENTS AND DISCLOSURES

The work was supported by UMKC School of Pharmacy Dean internal bridge/seed funds. The authors acknowledge Gattefossé Corporation (Saint-Priest, France) for providing a gift sample of Labrafac CC oil. We gratefully acknowledge Mr. Jack Liu (Zhenjiang Dong Yuan Biotech Co., Ltd., Jiangsu, China) for providing samples of hyaluronic acid. We also thank Richard Hastings at Kansas University for his assistance with the flow cytometry analysis. We are grateful to Dr. Jeffrey L. Price for providing assistance with the confocal laser scanning microscopy at the University of Missouri, Kansas City; School of Biological Sciences. The authors appreciate the helpful discussions on ROS and GSH assay with Dr. Miezan JM Ezoulin (Post-doctoral research associate at the University of Missouri Kansas City; School of Pharmacy. The assistance of Jianing Meng (Graduate student at the University of Missouri Kansas City School of Pharmacy) for the figure graphic design is appreciated. The authors thank Barbara Fegley for her assistance with the Electron microscopy at University of Kansas Medical Center, Kansas City, Kansas.

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Authors and Affiliations

  1. Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA

    Ibrahima Youm, Vivek Agrahari & Bi-Botti C. Youan

  2. Department of Geosciences, University of Missouri-Kansas City, 420 Flarsheim Hall, 5110 Rockhill Rd., Kansas City, Missouri, 64110, USA

    James B. Murowchick

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  1. Ibrahima Youm
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Correspondence to Bi-Botti C. Youan.

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Table S1

Independent, dependent variables and coded values of the experimental design of docetaxel-loaded hyaluronic acid grafted nanocapsules (DOCX 15.4 kb)

Fig. S1

Evaluation of the particle mean diameter of docetaxel-loaded Hyaluronic acid-grafted NCs before and after freeze-drying (n = 3, mean ± SD). (JPEG 102 kb)

High Resolution Image (TIFF 52.8 kb)

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Youm, I., Agrahari, V., Murowchick, J.B. et al. Uptake and Cytotoxicity of Docetaxel-Loaded Hyaluronic Acid-Grafted Oily Core Nanocapsules in MDA-MB 231 Cancer Cells. Pharm Res 31, 2439–2452 (2014). https://doi.org/10.1007/s11095-014-1339-x

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  • DOI: https://doi.org/10.1007/s11095-014-1339-x

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