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

doi:10.1016/j.nano.2017.03.001

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 journal › Article › peer-review

496 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 language	English
Pages (from-to)	1627-1636
Number of pages	10
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	13
Issue number	5
DOIs	https://doi.org/10.1016/j.nano.2017.03.001
State	Published - Jul 2017

Bibliographical note

Publisher Copyright:
© 2017

Funding

Funding: This work was supported by the USPHS grant R41-CA-189517 and KSTC-184-512-15-209, and, in part, by Agnes Brown Duggan Endowment and Helmsley Trust Fund, awarded to RCG. Ramesh Gupta holds the Agnes Brown Duggan Chair in Oncological Research.

Funders	Funder number
Agnes Brown Duggan Endowment
Helmsley Trust Fund
National Childhood Cancer Registry – National Cancer Institute	R41CA189517
National Childhood Cancer Registry – National Cancer Institute
U.S. Public Health Service	KSTC-184-512-15-209, R41-CA-189517
U.S. Public Health Service

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.nano.2017.03.001

Cite this

@article{e2b79b858d094008b263c5f40cf93ae4,

title = "Milk-derived exosomes for oral delivery of paclitaxel",

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 \textasciitilde{}108 nm, a narrow particle size distribution (PDI \textasciitilde{}0.190), zeta potential (\textasciitilde{} −7 mV) and a practical loading efficiency of \textasciitilde{}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",

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

note = "Publisher Copyright: {\textcopyright} 2017",

year = "2017",

month = jul,

doi = "10.1016/j.nano.2017.03.001",

language = "English",

volume = "13",

pages = "1627--1636",

number = "5",

}

TY - JOUR

T1 - Milk-derived exosomes for oral delivery of paclitaxel

AU - Agrawal, Ashish K.

AU - Aqil, Farrukh

AU - Jeyabalan, Jeyaprakash

AU - Spencer, Wendy A.

AU - Beck, Joshua

AU - Gachuki, Beth W.

AU - Alhakeem, Sara S.

AU - Oben, Karine

AU - Munagala, Radha

AU - Bondada, Subbarao

AU - Gupta, Ramesh C.

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

KW - Antitumor efficacy

KW - Exosomes

KW - Immunological responses

KW - Lung cancer

KW - Systemic toxicity

KW - Taxol

UR - https://www.scopus.com/pages/publications/85019709730

UR - https://www.scopus.com/inward/citedby.url?scp=85019709730&partnerID=8YFLogxK

U2 - 10.1016/j.nano.2017.03.001

DO - 10.1016/j.nano.2017.03.001

M3 - Article

C2 - 28300659

AN - SCOPUS:85019709730

SN - 1549-9634

VL - 13

SP - 1627

EP - 1636

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

IS - 5

ER -

Milk-derived exosomes for oral delivery of paclitaxel

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this