TY - JOUR
T1 - Convenient formulation and application of a supramolecular ureido-pyrimidinone modified poly(ethylene glycol) carrier for intrarenal growth factor delivery
AU - Dankers, P.Y.W.
AU - van Luyn, M.J.A.
AU - Huizinga-van der Vlag, A.
AU - Petersen, A.H.
AU - Koerts, J.A.
AU - Bosman, A.W. (Tonny)
AU - Popa, E.R.
PY - 2015/7/2
Y1 - 2015/7/2
N2 - The development of local, intrarenal drug delivery therapies is imperative to induce a therapeutic effect without the requirement of high concentrations of drugs, thereby diminishing systemic side effects. Hydrogels are eminently suitable as drug delivery carriers in soft tissues. Here, we show that a supramolecular hydrogel carrier based on ureido-pyrimidinone (UPy) modified poly(ethylene glycol) can be easily formulated and conveniently be applied to deliver anti-inflammatory and anti-fibrotic growth factor protein BMP7 to the kidney. Short-term, immediate modulation of renal inflammation and extracellular matrix remodelling is shown in a rat model of acute kidney injury. Induction of ischemia/reperfusion injury was followed by renal subcapsular implantation of pristine and BMP7-loaded supramolecular hydrogels. The cortical area under the site of implantation was studied after 3 and 7 days. Subcapsular delivery of only 0.30 μg BMP7 from these supramolecular hydrogels led to a significant reduction in interstitial inflammatory and myofibroblast cell numbers at the site of implantation. These findings show that local, intrarenal delivery of an anti-inflammatory and anti-fibrotic drug from a supramolecular hydrogel carrier can be effective in the reduction of acute inflammation and incipient fibrosis.
AB - The development of local, intrarenal drug delivery therapies is imperative to induce a therapeutic effect without the requirement of high concentrations of drugs, thereby diminishing systemic side effects. Hydrogels are eminently suitable as drug delivery carriers in soft tissues. Here, we show that a supramolecular hydrogel carrier based on ureido-pyrimidinone (UPy) modified poly(ethylene glycol) can be easily formulated and conveniently be applied to deliver anti-inflammatory and anti-fibrotic growth factor protein BMP7 to the kidney. Short-term, immediate modulation of renal inflammation and extracellular matrix remodelling is shown in a rat model of acute kidney injury. Induction of ischemia/reperfusion injury was followed by renal subcapsular implantation of pristine and BMP7-loaded supramolecular hydrogels. The cortical area under the site of implantation was studied after 3 and 7 days. Subcapsular delivery of only 0.30 μg BMP7 from these supramolecular hydrogels led to a significant reduction in interstitial inflammatory and myofibroblast cell numbers at the site of implantation. These findings show that local, intrarenal delivery of an anti-inflammatory and anti-fibrotic drug from a supramolecular hydrogel carrier can be effective in the reduction of acute inflammation and incipient fibrosis.
KW - Drug delivery/release
KW - Formulation
KW - Growth factor
KW - Kidney
KW - Supramolecular hydrogel
UR - http://www.scopus.com/inward/record.url?scp=84945467912&partnerID=8YFLogxK
U2 - 10.1016/j.eurpolymj.2015.07.010
DO - 10.1016/j.eurpolymj.2015.07.010
M3 - Article
AN - SCOPUS:84945467912
SN - 0014-3057
VL - 72
SP - 484
EP - 493
JO - European Polymer Journal
JF - European Polymer Journal
ER -