Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Ther. 2014 Mar;22(3):522-534. doi: 10.1038/mt.2013.190. Epub 2013 Aug 13.

Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit.

Author information

1
James Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA. Electronic address: B0wang06@louisville.edu.
2
James Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
3
Department of Diagnostic Radiology, University of Louisville, Louisville, Kentucky, USA; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, Kentucky, USA.
4
Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
5
James Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA; Department of Microbiology & Immunology, University of Louisville, Louisville, Kentucky, USA; Louisville Veterans Administration Medical Center, Louisville, Kentucky, USA. Electronic address: H0Zhan17@louisville.edu.

Abstract

The gut mucosal immune system is considered to play an important role in counteracting potential adverse effects of food-derived antigens including nanovesicles. Whether nanovesicles naturally released from edible fruit work in a coordinated manner with gut immune cells to maintain the gut in a noninflammatory status is not known. Here, as proof of concept, we demonstrate that grapefruit-derived nanovesicles (GDNs) are selectively taken up by intestinal macrophages and ameliorate dextran sulfate sodium (DSS)-induced mouse colitis. These effects were mediated by upregulating the expression of heme oxygenase-1 (HO-1) and inhibiting the production of IL-1β and TNF-α in intestinal macrophages. The inherent biocompatibility and biodegradability, stability at wide ranges of pH values, and targeting of intestinal macrophages led us to further develop a novel GDN-based oral delivery system. Incorporating methotrexate (MTX), an anti-inflammatory drug, into GDNs and delivering the MTX-GDNs to mice significantly lowered the MTX toxicity when compared with free MTX, and remarkably increased its therapeutic effects in DSS-induced mouse colitis. These findings demonstrate that GDNs can serve as immune modulators in the intestine, maintain intestinal macrophage homeostasis, and can be developed for oral delivery of small molecule drugs to attenuate inflammatory responses in human disease.

PMID:
23939022
PMCID:
PMC3944329
DOI:
10.1038/mt.2013.190
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center