Optimising liposome-encapsulated praziquantel formulations for treating and overcoming resistant isolates of schistosoma mansoni

ABSTRACT

Praziquantel [pzq.] liposomes of [DPPC Cholesterol] molar ratio 72, neutral [N] and negatively [-ve] charged, were prepared by the vortex dispersion method yielding multilamellar vesicles [MLV]. Some MLV were sonicated yielding unilamellar vesicles [ULV]. Entrapped pzq. was measured using UV spectrophotometric analysis at 265 nm. [N] UL and ML liposomes exhibited higher percentage entrapment over the [-ve] liposomes. Swelling at 52° for 24 hours, led to increased percentage entrapment of UL pzq. liposomes. Transmission electron micrographing was employed to characterize ML liposomes. [N] pzq. liposomes, of higher percentage entrapment, were used in curative and prophylactic experiments against susceptible [S] and resistant [R] isolates of S. mansoni, in mice. Pzq. liposomes were injected subcutaneously [s.c.] to effect efficient targeting to the site of infection viz., the liver. The effect of pzq. liposomes, in half dose, was compared to the same dose of free pzq, administered orally and as s.c. injection, in addition to full oral free pzq. [1000 mg/kg]. The curative experiment showed best efficacy for full oral free pzq. On the other hand, [N] pzq. ML liposomes imparted the highest 7-days chemoprophylactic effect against both [S] and [R] isolates of S. mansoni, emphasizing the significant success of such a pharmaceutical formulation in conquering the [R] S. mansoni isolate [EE2] responsible for evolving resistance to pzq. curative effect, in the Egyptian population