RESUMO
In this study we present a novel silver complex of hyaluronan-lipoate (SHLS12) in a gel-state form. NMR analysis, conductometry and elemental analysis demonstrated stable non-covalent interactions between silver ions and the polysaccharide-lipoate backbone, whereas rheological investigations confirmed its gel-like physical-chemical behavior. Biological studies showed the ability of SHLS12 to exert a straightforward activity against different bacterial strains grown in sessile/planktonic state. The biocompatibility was also proved toward two eukaryotic cell lines. By considering both its ability to preserve antibacterial properties when exposed to the serum protein BSA and its low susceptibility to be degraded by hyaluronidase enzyme, this novel complex may be considered as a promising biomaterial for future in vivo applications.
Assuntos
Antibacterianos/síntese química , Materiais Biocompatíveis/síntese química , Ácido Hialurônico/análogos & derivados , Ácido Hialurônico/química , Ácido Tióctico/análogos & derivados , Ácido Tióctico/química , Células 3T3 , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Géis/síntese química , Géis/química , Géis/farmacologia , Humanos , Ácido Hialurônico/síntese química , Camundongos , Prata/química , Ácido Tióctico/síntese químicaRESUMO
The synthesis and physicochemical characterisation of mixed lipoic and formic esters of hyaluronan (Lipohyal) are presented in this paper. The synthesis was conducted by activating lipoic acid with 1,1'-carbonyldiimidazole to obtain lipoyl imidazolide, which reacted with hyaluronan (HA) in formamide under basic conditions. This procedure allows researchers to modulate easily the degree of substitution over a range of 0.05-1.8. Radical scavenger properties were analysed by UV-vis spectroscopy, where improved performance was demonstrated for Lipohyal with respect to the HA row material and lipoic acid. The chemical modification also causes HA to show an improved resistance to hyaluronidase digestion. These findings show that Lipohyal is a highly interesting derivative for applications in the tricological and dermo-cosmetic field and as an anti-aging ingredient. Moreover, Lipohyal can be easily crosslinked by UV irradiation, resulting in an innovative hydrogel with distinctive viscoelastic properties that is suitable as both a dermal-filler and as an intra-articular medical device.
Assuntos
Fenômenos Químicos , Ácido Hialurônico/análogos & derivados , Ácido Tióctico/química , Animais , Biocatálise , Reagentes de Ligações Cruzadas , Formamidas/química , Sequestradores de Radicais Livres/química , Ácido Hialurônico/química , Ácido Hialurônico/fisiologia , Hialuronoglucosaminidase/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Imidazóis/química , Espectroscopia de Infravermelho com Transformada de Fourier , Ácido Tióctico/análogos & derivados , Raios Ultravioleta , ViscosidadeRESUMO
Imidazolium trans-tetrachloro(dimethylsulfoxide)imidazoleruthenium(III) (NAMI-A) is a novel ruthenium complex with selective activity against metastases currently in Phase I clinical trials in the Netherlands. Pharmaceutical quality control of NAMI-A drug substance and lyophilized product warranted the development of an assay for determination and quantification of NAMI-A and degradation products. A high performance liquid chromatography (HPLC) method was developed, consisting of a C18 column with 0.50 mM sodium dodecylsulfate in 3% methanol at pH 2.5 (acidified using trifluoromethanesulfonic acid) as the mobile phase and UV-detection at 358 nm. The HPLC method was proven to be linear, accurate and precise. Stress testing showed that degradation products were separated from the parent compound. By combining results of nuclear magnetic resonance (NMR) and HPLC experiments, one degradation product was identified as the mono-hydroxy species of NAMI-A. HPLC analysis with off-line detection of the eluate with flameless atomic absorption spectrometry (F-AAS) showed that under most conditions, all ruthenium-containing compounds show a peak in the HPLC chromatogram and that all ruthenium applied to the column is recovered quantitatively. For completely degraded solutions of NAMI-A some ruthenium is retained on the column. Suitability of the HPLC method for the pharmaceutical quality control of NAMI-A lyophilized product was demonstrated.