Liposomal formulations of prilocaine: effect of complexation with hydroxypropyl-ß-cyclodextrin on drug anaesthetic efficacy

A combined strategy, based on cyclodextrin complexation and loading in liposomes, has been investigated to develop a new delivery system with improved therapeutic activity of the local anesthetic, prilocaine (PRL). In order to evaluate the actual effectiveness and advantages of this approach compared to the traditional drug-in-liposome one, four different liposomal formulations were prepared: (1) liposomes loaded with PRL base as complex with hydroxypropyl-beta-cyclodextrin (HP CD) in the aqueous phase; (2) liposomes loaded with PRL hydrochloride in the aqueous phase; (3) liposomes loaded with PRL base in the lipophilic phase; and (4) "double-loaded" liposomes, containing free PRL base in the membrane bilayer and its HP CD complex in the aqueous compartment. All batches were characterized for particle size, charge, deformability, and entrapment efficiency from using, respectively, light scattering, extrusion, and dialysis techniques, while the anesthetic effect was evaluated in vivo on Guinea pigs, according to the test of dorsal muscle contraction. All drug liposomal dispersions showed enhanced analgesic duration with respect to the corresponding aqueous solutions, but significant differences were observed between the different formulations. In particular, cyclodextrin complexation not only allowed an efficient encapsulation of PRL base in the aqueous vesicle core, but also increased the anesthetic effect duration and reduced the initial lag time, in comparison with the corresponding formulations containing, respectively, free PRL in the lipophilic phase or PRL hydrochloride in the aqueous vesicle core. The technique of double loading was the most effective, giving rise to the shortest onset time and longest duration of anesthetic effect.