PH SENSITIVITY AND PLASMA STABILITY OF LIPOSOMES CONTAINING N-STEAROYLCYSTEAMINE

In this study, we investigated the pH sensitivity of different liposom al formulations containing 10 mol% N-stearoylcys-teamine, as pH sensit ive molecule. Liposome stability was monitored by determining the rele ase of different entrapped water soluble molecules, 5,6-carboxyfluores cein (CF) being the marker of leakage mainly used. Small unilamellar v esicles composed of egg phosphatidylcholine (EPC) and N-stearoylcystea mine (9:1 molar ratio) incubated at 20 degrees C in citrate phosphate buffer released, at pH 6.8, 2.5 fold the amount of CF released at pH 7 .4. The addition of plasma to the incubation medium and an increase of temperature to 37 degrees C led to significantly increased the CF rel ease from EPC/N-stearoylcysteamine SUV, both at pH 7.4 and 6.8, The ad dition of cholesterol had a stabilizing effect on liposomal vesicles w ith respect to both temperature and plasma, without affecting pH sensi tivity. In fact, at 37 degrees C and in 25% plasma the ternary mixture showed the highest CF release, as a consequence of the moderate acidi fication of the medium from 7.4 to 6.8. Thus, these liposome formulati ons are potentially a useful tool for specific drug delivery to pathol ogical tissues such as tumours, inflammation sites and ischemic areas where it is known that a lowering of the pH can occur. (C) 1997 Elsevi er Science B.V.