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Nanomedicine. 2017 Jul;13(5):1627-1636. doi: 10.1016/j.nano.2017.03.001. Epub 2017 Mar 11.

Milk-derived exosomes for oral delivery of paclitaxel.

Author information

1
James Graham Brown Cancer Center, University of Louisville, Louisville, KY.
2
James Graham Brown Cancer Center, University of Louisville, Louisville, KY; Department of Medicine, University of Louisville, Louisville, KY.
3
Department of Medicine, University of Louisville, Louisville, KY.
4
3P Biotechnologies, Inc., Louisville, KY.
5
Department of Microbiology, Immunology & Molecular Genetics, and Markey Cancer Center, University of Kentucky, Lexington, KY.
6
James Graham Brown Cancer Center, University of Louisville, Louisville, KY; 3P Biotechnologies, Inc., Louisville, KY; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY. Electronic address: rcgupta@louisville.edu.

Abstract

In this report milk-derived exosomes have been investigated for oral delivery of the chemotherapeutic drug paclitaxel (PAC) as an alternative to conventional i.v. therapy for improved efficacy and reduced toxicity. PAC-loaded exosomes (ExoPAC) were found to have a particle size of ~108 nm, a narrow particle size distribution (PDI ~0.190), zeta potential (~ -7 mV) and a practical loading efficiency of ~8%. Exosomes and ExoPAC exhibited excellent stability in the presence of simulated-gastrointestinal fluids, and during the storage at -80 °C. A sustained release of PAC was also observed up to 48 h in vitro using PBS (pH 6.8). Importantly, ExoPAC delivered orally showed significant tumor growth inhibition (60%; P<0.001) against human lung tumor xenografts in nude mice. Treatment with i.p. PAC at the same dose as ExoPAC, however, showed modest but statistically insignificant inhibition (31%). Moreover, ExoPAC demonstrated remarkably lower systemic and immunologic toxicities as compared to i.v. PAC.

KEYWORDS:

Antitumor efficacy; Exosomes; Immunological responses; Lung cancer; Systemic toxicity; Taxol

PMID:
28300659
DOI:
10.1016/j.nano.2017.03.001
[Indexed for MEDLINE]

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