Supramolecular citrate poly allylamine hydrochloride nanoparticles for citrate delivery and calcium oxalate nanocrystal dissolution

Abstract

Hypothesis: Renal calculi (kidney stones) are mainly made by calcium oxalate and can causedifferent complications including malfunction of the kidney. The most important urinary stoneinhibitors are citrate molecules. Unfortunately, the amount of citrate reaching the kidney afteroral ingestion is low. We hypothesized that nanoparticles of polyallylamine hydrochloride (CIT-PAH) carrying citrate ions could simultaneously deliver citrates while PAH would complexoxalate triggering dissolution and removal of CaOx nanocrystals.Experiments: We successfully prepared nanoparticles of citrate ions with polyallylaminehydrochloride (CIT-PAH), PAH with oxalate (OX-PAH) and characterize them by Small AngleX ray Scattering (SAXS), Transmission Electron Microscopy (TEM), Dynamic Light Scattering(DLS) and NMR. Dissolution of CaOx nanocrystals in presence of CIT-PAH have been followed with Wide Angle Xray Scattering (WAXS), DLS and Confocal Raman Microscopy.Raman spectroscopy was used to study the dissolution of crystals in synthetic urine samples. Therelease of citrate from CIT-PAH was followed by diffusion NMR. Molecular dynamics (MD)simulations were carried out to study the interaction of CIT and OX ions with PAH.Findings: CIT-PAH nanoparticles dissolves CaOx nanocrysPAH.as shown by NMR, DLS, TEMand WAXS in water and by Raman spectroscopy in artificial human urine. WAXS and Ramanshow that the crystal structure of CaOx disappears in the presence of CIT-PAH. DLS shows thatthe time required for CaOX dissolution will depend on the concentration of CIT-PAH NPs.NMR proves that citrate ions are released from the CIT PAH NPs during CaOX dissolution, MDsimulations showed that oxalates exhibit a stronger interaction for PAH than citrate, explainingthe removal of oxalate ions and replacement of the citrate in the polymer nanoparticles.