Local release of tacrolimus from hydrogel-based drug delivery system is controlled by inflammatory enzymes in vivo and can be monitored non-invasively using in vivo imaging

PloS One
Dzhuliya V DzhonovaRobert Rieben

Abstract

Local drug delivery systems that adjust the release of immunosuppressive drug in response to the nature and intensity of inflammation represent a promising approach to reduce systemic immunosuppression and its side effects in allotransplantation. Here we aimed to demonstrate that release of tacrolimus from triglycerol monostearate hydrogel is inflammation-dependent in vivo. We further report that by loading the hydrogel with a near-infrared dye, it is possible to monitor drug release non-invasively in an in vivo model of vascularized composite allotransplantation. Inflammation was induced by local challenge with lipopolysaccharides in naïve rats 7 days after injection of tacrolimus-loaded hydrogel in the hind limb. Tacrolimus levels in blood and tissues were measured at selected time points. A near-infrared dye was encapsulated in the hydrogel together with tacrolimus in order to monitor hydrogel deposits and drug release in vitro and in vivo in a model of vascularized composite allotransplantation. Injection of lipopolysaccharides led to increased blood and skin tacrolimus levels (p = 0.0076, day 7 vs. day 12 in blood, and p = 0.0007 in treated limbs, 48 h after injection compared to controls). Moreover, lipopolysaccharides-in...Continue Reading

References

Nov 19, 2005·Journal of Biomedical Optics·Sharon BlochSamuel Achilefu
Feb 21, 2009·Plastic and Reconstructive Surgery·Mario G SolariW P Andrew Lee
Jul 21, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·T WangA S Chong
Oct 11, 2011·Transplant International : Official Journal of the European Society for Organ Transplantation·Arnaud CapronPierre Wallemacq
Apr 28, 2012·Biomaterials·Daisuke AsaiAshutosh Chilkoti
Aug 15, 2014·Science Translational Medicine·Thusitha GajanayakeEsther Vögelin
Jan 26, 2017·Plastic and Reconstructive Surgery·Jignesh V UnadkatAlexander M Spiess
Oct 8, 2017·The Journal of Surgical Research·Radu OlariuAdriano Taddeo
Aug 4, 2018·Current Opinion in Organ Transplantation·Adriano TaddeoRobert Rieben

❮ Previous
Next ❯

Citations

Dec 12, 2018·Current Opinion in Organ Transplantation·Branislav KollarLeonardo V Riella
Oct 31, 2019·Biomaterials Science·Abdollah Zakeri SiavashaniMarkus Rottmar
May 13, 2021·ACS Biomaterials Science & Engineering·Yuxi C DongDavid P Cormode

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
biopsy
fluorescence imaging

Software Mentioned

Prism
TGMS
ARRIVE
TAC
Power
TargetLynx
Pannoramic Viewer
MassLynx
3R
GraphPad

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here