Interaction between sodium hyaluronate and tetracyclines

Abstract

The interaction between sodium hyaluronate (HA) and 6 kinds of tetracycline (TCs) was investigated by dissolution tests, conductivity, viscosity and turbidity measurements. The 6 TCs were tetracycline (TEC), oxytetracycline (OTC), doxycycline (DOC), methacycline (METC), minocycline (MINC) and chlortetracycline (CTC). In dissolution tests, the release of TCs from the HA solution contained in the cellulose tube was measured and it was found that the 50% release time (T50) of TCs was prolonged with the increase of HA concentration. And the dependence of T50 on HA concentration was different in TCs: the release of METC was most delayed and that of OTC was least affected. By measuring the conductivity of TCs solutions, the binding of TCs to HA was suggested. In viscosity measurements of the HA solution at various pHs, the increase of viscosity was observed by the addition of METC. However in the case of OTC such an increase was not observed. The dissolution tests at various pHs were further tried and the release rate of METC depended on the pH, while that of OTC showed no dependency. Finaly, it was found that T50 of TCs from the HA solution correlates well with the literature values of apparent partition coefficients of TCs between n-octanol and aqueous buffers. Comparing T50 of 6 TCs from carboxymethylchitin (DS = 0.56) solution, it was clarified that the lipophilicity of TCs are more effective to retard the release in the case of the HA solution. From the above results, an electrostatic interaction between HA and TCs can be assumed to be almost similar among 6 TCs.(ABSTRACT TRUNCATED AT 250 WORDS)