Milk-derived exosomes for oral delivery of paclitaxel

Ashish K. Agrawal, Farrukh Aqil, Jeyaprakash Jeyabalan, Wendy A. Spencer, Joshua Beck, Beth W. Gachuki, Sara S. Alhakeem, Karine Oben, Radha Munagala, Subbarao Bondada, Ramesh C. Gupta

Research output: Contribution to journalArticlepeer-review

389 Scopus citations

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.

Original languageEnglish
Pages (from-to)1627-1636
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume13
Issue number5
DOIs
StatePublished - Jul 2017

Bibliographical note

Publisher Copyright:
© 2017

Keywords

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

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • General Materials Science
  • Pharmaceutical Science

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