IN-VITRO IN-VIVO MYOTOXICITY OF INTRAMUSCULAR LIPOSOMAL FORMULATIONS

Purpose, The first objective was to study the in vitro myotoxicity of empty liposomes and to examine whether liposome size, charge and fluid ity affect liposome myotoxicity. The second objective was to investiga te the effect of liposomal encapsulation on the in vitro and in vice m yotoxicity of loxapine compared to the loxapine commercial preparation (Loxitane(R)). Methods. The in vitro myotoxicity of empty liposomes a nd loxapine liposomes was evaluated by the cumulative efflux of the cy tosolic enzyme creatine kinase (CK) from the isolated rat extensor dig itorum longus (EDL) muscle over a 2 hour period. In the in vivo studie s, the area under plasma CK curve over 12 hours was used to evaluate m uscle damage. Results. The in vitro myotoxicity for all empty liposoma l formulations was not statistically different from negative controls (untreated control muscles and normal saline injected muscles). Howeve r, these empty liposomal formulations were significantly less myotoxic than the positive controls (muscles injected with phenytoin and muscl e sliced in half). In vitro-in vivo studies showed that the liposomal encapsulation of loxapine resulted in significant (P < 0.05) reduction in myotoxicity (80% in vitro and 60% in vivo) compared to the commerc ially available formulation which contains propylene glycol (70% V/V) and polysorbate 80 (5% W/V) prepared at equal concentration. Conclusio ns, Results indicate that empty liposomes do not induce myotoxicity. F urthermore, liposomal size, charge and fluidity do not affect myotoxic ity. In addition, in vitro and in vivo studies have demonstrated that liposomal encapsulation of loxapine can reduce myotoxicity compared to a formulation containing organic cosolvents.