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Exosomes for the Enhanced Tissue Bioavailability and Efficacy of Curcumin

  • Research Article
  • Theme: Therapeutic and Diagnostic Applications of Exosomes and other Extracellular Vesicles
  • Published:
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Abstract

Exosomes are extracellular microvesicles with a particle size of 30–100 nm and carry a cargo of proteins, lipids, RNA, and DNA. Their properties of shuttling in-and-out of the cells suggest that these particles can be exploited as a nano drug carrier. In this manuscript, we show that curcumin can be delivered effectively using milk-derived exosomes. Curcumin when mixed with exosomes in the presence of 10% ethanol:acetonitrile (1:1) provided a drug load of 18–24%, and the formulation stored at − 80°C was stable for 6 months as determined by particle size analysis, drug load, and antiproliferative activity. The uptake of exosomes by cancer cells involved caveolae/clathrin-mediated endocytosis. Oral administration of exosomal curcumin (ExoCUR) in Sprague-Dawley rats demonstrated 3–5 times higher levels in various organs versus free agent. ExoCUR showed enhanced antiproliferative activity against multiple cancer cell lines including, breast, lung, and cervical cancer compared with the free curcumin. ExoCUR showed significantly higher anti-inflammatory activity measured as NF-κB activation in human lung and breast cancer cells. To determine in vivo antitumor activity, nude mice bearing the cervical CaSki tumor xenograft were treated with ExoCUR by oral gavage, curcumin diet, exosomes alone, and PBS as controls. While curcumin via dietary route failed to elicit any effect, exosomes had a modest (25–30%) tumor growth inhibition. However, ExoCUR showed significant inhibition (61%; p < 0.01) of the cervical tumor xenograft. No gross or systemic toxicity was observed in the rats administered with the exosomes or ExoCUR. These results suggest that exosomes can be developed as potential nano carriers for delivering curcumin which otherwise has encountered significant tissue bioavailability issues in the past.

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Acknowledgements

We are thankful to Dr. Manicka V. Vadhanam for useful discussions and help with the animal studies. Curcumin used in this study was generously provided by Sabinsa Corp.

Funding

This work was supported by Agnes Brown Duggan Endowment and Helmsley Trust Funds, awarded to R.C.G.

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Authors and Affiliations

  1. Department of Medicine, University of Louisville, Louisville, Kentucky, 40202, USA

    Farrukh Aqil & Radha Munagala

  2. James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, USA

    Farrukh Aqil, Radha Munagala, Jeyaprakash Jeyabalan, Ashish Kumar Agrawal & Ramesh Gupta

  3. Department of Pharmacology and Toxicology, University of Louisville, Delia Baxter II, Room 304E, 580 S. Preston Street, Louisville, Kentucky, 40202, USA

    Ramesh Gupta

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  1. Farrukh Aqil
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Correspondence to Ramesh Gupta.

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Animals were maintained under a 12-h light/12-h dark cycle in accordance with the Institutional Animal Care and Use Committee (IACUC) guidelines. All the animal experiments were conducted in full compliance with local, national, ethical, and regulatory principles and local licensing regulations, per the spirit of Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) expectations for animal care and use/ethics.

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Aqil, F., Munagala, R., Jeyabalan, J. et al. Exosomes for the Enhanced Tissue Bioavailability and Efficacy of Curcumin. AAPS J 19, 1691–1702 (2017). https://doi.org/10.1208/s12248-017-0154-9

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