Developing poly(ethylene glycol)-b-poly(β-hydroxybutyrate)-based self-assembling prodrug for the management of cisplatin-induced acute kidney injury
Duc Tri Bui, Yukio Nagasaki
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.
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…
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Taxonomy
TopicsChemotherapy-induced organ toxicity mitigation · Pharmacological Effects and Toxicity Studies · Electrolyte and hormonal disorders