Development, characterization and in vivo evaluation of benzocaine-loaded liposomes

This study reports the development and in vivo evaluation of a liposomal formulation of the local anaesthetic benzocaine. Multi-lamellar (MLV) and small uni-lamellar (SUV) vesicles entrapping benzocaine were prepared using 50:50 w/w phosphatidylcholine-cholesterol as lipophilic phase and 50:50 v/v ethanol-water as hydrophilic phase. Liposome size, Zeta-potential, encapsulation efficiency and skin penetration properties were determined. Drug permeation from liposomal dispersions, as such or formulated in Carbopol gel, was evaluated through artificial lipophilic membranes and excised abdominal rat skin, whereas in vivo anaesthetic effect was tested on rabbits. Interestingly, addition of the drug into the hydrophilic phase, rather than into the lipophilic one, during liposome preparation enabled an improvement of the MLV's entrapment efficiency from 29.7% to 82.3%. On the other hand, sonication conditions to obtain SUV influenced size and polydispersity index of the vesicles and reduced the entrapment efficiency by about 30%. All liposomal-benzocaine formulations showed sustained release properties and a more intense anaesthetic effect than plain drug. Permeation experiments from drug solutions in gel containing the same amount of ethanol as in the liposomal formulations made it possible to exclude a possible enhancer effect of this solvent, at least when not used in liposomal formulations. MLV with the drug added into the hydrophilic phase gave the most effective formulation, showing a permeability coefficient value 2.5 times higher than that of the plain drug and allowing a significant improvement (P<0.01) not only of intensity but also of duration of anaesthetic effect of benzocaine. These results suggest that a suitably developed liposomal formulation of benzocaine can be of actual value for improving its clinical effectiveness in topical anaesthesia.