Liposomal formulation of netilmicin

Netilmicin, a semisynthetic aminoglycoside (Wright, J.J., J. Chem. Sec. Chem. Commun., 6 (1976) 206-208), was encapsulated in two different kinds of liposomes: simplified dehydration-rehydration vesicles and extruded vesicles. These formulations were characterized and their behaviour was evaluated in one animal model. Liposomal netilmicin formulations, prepared with the lipid composition phosphatidylcholine:cholesterol:phosphatidylinositol in a molar ratio of 5:1:4, exhibit high encapsulation efficiencies (> 65%) and high drug/lipid ratios ( > 32 mu g/mu mol), without alteration of in vitro biological activity. A substantial reduction of in vivo acute toxicity Was found for liposomal netilmicin (LD(50) > 50 mg/kg) compared with the free form (LD(50) = 20-28 mg/kg). The half-life circulation time of liposomal netilmicin formulations was greatly prolonged (12-18-fold) compared to the free form. The increase of liposomal netilmicin pharmacological activity was evaluated by the increase of survival in an in vivo model of peritonitis infection (from 33% to 83% prophylactically and from 17% to 50% therapeutically). The increase on the therapeutic index of liposomal netilmicin, suggests the possibility of reduction the frequency of administration and monitorization of netilmicin as well as safety during prolonged treatments. (C) 1997 Elsevier Science B.V.