Convenient formulation and application of a supramolecular ureido-pyrimidinone modified poly(ethylene glycol) carrier for intrarenal growth factor delivery

• Easy formulation of growth factor drug-loaded supramolecular hydrogel.
• Beneficial effect of local intrarenal drug delivery.
• Proposed relatively low amount of drug needed for beneficial effect.

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.

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