The dissolution of mono-sodium urate monohydrate crystals: formulation of a biocompatible buffer solution with potential use in the treatment of gouty arthropaties

摘要

The dissolving abilities (DAs) of several aqueous media for microcrystalline mono-sodium urate monohydrate (MSU, NaC5N4O3H3·H2O) have been investigated using UV spectrophotometry for quantitative analytical determinations and X-ray diffrac-tion, scanning electron microscopy and polar-ized light optical microscopy to assess struc-tural aspects. High DAs were found for a buffer labeled TMT which contains tris(hydrox-ymethyl)aminomethane (TRIS), tris(hydrox-ymethyl)aminomethane hydrochloride (TRIS·HCl), D-mannitol (MAN) and taurine (TAU) and gave DA 30 =1298(5) mg/L for syn-thetic MSU after 30 min incubation at 37°C and pH 7.4, most of the dissolution taking place within the first 5-10 min. Semiempirical molecular modelling techniques (ZINDO/1) show a favorable energy balance for the forma-tion of a TRIS-urate-TRIS adduct which might explain the high DA values. Buffers containing linear or dendrimeric polyamines gave DA val-ues which suggest that complex formation toward sodium cations is less important. An ex vivo MSU sample was found to have a signifi-cantly lower DA value (DA 30 =1124(5) mg/L in TMT) as well as a lower crystallinity than its synthetic counterpart, possibly related to the presence of a non-crystalline impurity such as endogenous proteins. Cytotoxicity tests based on the MTT assay were used to check the bio-compatibility of the TMT buffer and showed only moderate cell mortality after 24 h contact with the buffer solution.