Interactions of hyaluronan with oppositely charged surfactants in very diluted solutions in water.

The phase behavior of aqueous systems containing hyaluronan, at concentrations between 2 and 100 mg/L, and oppositely charged surfactants was investigated. A fluorescence probe technique revealed the formation of micellar structures on the hyaluronan in homogeneous systems well below the surfactant standard, critical, micellar concentration. Moreover, regions of gel-phase separation were revealed. A detailed phase diagram was, thus, constructed in the very diluted region and the hyaluronan concentration was found to be the main parameter controlling the phase behavior, in contrast to the charge ratio. The stability of hyaluronan-surfactant aggregates in the homogeneous systems while in storage at 4 °C (up to three months), against dilution, salt addition and on heating-cooling (between 10 and 50 °C) was also investigated. The aggregates were stable while in storage or upon increasing and decreasing the temperature. The dilution of hyaluronan-surfactant complexes or the addition of 0.15 M NaCl led to their disintegration. Finally, systems prepared in a 0.15 M NaCl solution showed that interactions are suppressed and no aggregation below the standard critical micellar concentration was observed.

Hyaluronic acid in complexes with surfactants: The efficient tool for reduction of the cytotoxic effect of surfactants on human cell types.

The cationic surfactants carbethoxypendecinium bromide (Septonex) and cetyltrimethylammonium bromide (CTAB) are known to be harmful for certain cell types (bacteria, fungi, mammal cells, etc.). Colloidal complexes of these surfactants with negatively-charged hyaluronic acid (HyA) were prepared for potential drug and/or universal delivery applications. The complexes were tested for their cytotoxic effect on different human cell types - osteoblasts, keratinocytes and fibroblasts. Both the CTAB-HyA and Septonex-HyA complexes were found to reduce the cytotoxicity induced by surfactants alone concerning all the tested concentrations. Moreover, we suggested the limits of HyA protection provided by the surfactant-HyA complexes, e.g. the importance of the amount of HyA applied. We also determined the specific sensitivity of different cell types to surfactant treatment. Keratinocytes were more sensitive to CTAB, while osteoblasts and fibroblasts were more sensitive to Septonex. Moreover, it was indirectly shown that CTAB combines lethal toxicity with cell metabolism induction, while Septonex predominantly causes lethal toxicity concerning fibroblasts. This comprehensive study of the effect of surfactant-HyA complexes on various human cell types revealed that HyA represents a useful CTAB or Septonex cytotoxic effect modulator at diverse levels. Potential applications for these complexes include drug and/or nucleic acid delivery systems, diagnostic dye carriers and cosmetics production.