# Developing poly(ethylene glycol)-b-poly(β-hydroxybutyrate)-based self-assembling prodrug for the management of cisplatin-induced acute kidney injury

## TL;DR

Researchers created nanoparticles that slowly release a ketone body to protect against kidney damage from chemotherapy.

## Contribution

A novel self-assembling prodrug nanoparticle that sustains β-hydroxybutyrate release for improved therapeutic efficacy.

## Key findings

- NanoBHB nanoparticles sustain BHB release in vitro and in vivo with low toxicity.
- NanoBHB provides superior nephroprotection in cisplatin-induced kidney injury compared to low-molecular-weight BHB.
- The nanoparticles can be administered orally or via injection.

## Abstract

Although β-hydroxybutyrate (BHB), one of the endogenous body ketones, possesses high bioactivities, it is rapidly consumed, metabolized, and eliminated from the body. In this study, we designed new self-assembling nanoparticles that sustainably released BHB to improve bioavailability and evaluated their efficacy in in vivo experiments using rodent animal models. Since poly(β-hydroxybutyrate) [poly(BHB)] is regarded as a polymeric prodrug that is hydrolyzed by endogenous enzymes and releases BHB in a sustained manner, our idea was to engineer hydrophobic poly(BHB) in one of the segments in the amphiphilic block copolymer, of which self-assembles in water to form nanoparticles of tens of nanometers in size (abbreviated as NanoBHB). Here, methoxy-poly(ethylene glycol) was employed as the hydrophilic segment of the block copolymer to stabilize the nanoparticles in aqueous environments, thus enabling NanoBHBs to be administrable both orally and through injection. Experimental results showed that NanoBHB has low toxicity and releases free BHB for an extended period in vitro and in vivo. Moreover, NanoBHB exhibits superior nephroprotective effects in cisplatin-induced acute kidney injury mouse models compared to low-molecular-weight (LMW) sodium BHB, suggesting the potential of NanoBHB as a sustainable release formulation to supply BHB for medicinal applications.

We engineered self-assembling poly(ethylene glycol)-b-poly(D,L-β-hydroxybutyrate) nanoparticles as a prodrug for continuous release of β-hydroxybutyrate, inducing bioactivity as a ketone body and providing nephroprotective properties against acute kidney injuries