In vitro and in vivo evaluation of a novel lidocaine-loaded cubosomal gel for prolonged local anesthesia.

Abstract

Marketed lidocaine dosage forms (such as ointment, gels, and injections) used to manage acute and chronic pain showed a short duration of action (<2 h). In this study, a lidocaine-loaded cubosomal gel was prepared to sustain the release of lidocaine to prolong the local anesthetic effect (high drug retention in the skin). Lidocaine-loaded cubosomal gels were prepared by melt emulsification and sonication using Pluronic F127 and DL-α-monoolein (at different levels). The cubosomal gels were characterized by morphology, size, zeta potential, entrapment efficacy, assay, viscosity, pH, and texture profiles. Ex vivo lidocaine permeation and retention studies were performed using Sprague-Dawley rat skin. Transmission electron microscopy images confirmed the bi-continuous liquid crystalline phase with a honeycomb cubosome structure. The cubosomal particle size (103-227nm), viscosity (13,524-15,627cp), and entrapment efficacy (78.4-94.7%) increase with the level of monoolein. The ex-vivo permeation study showed a biphasic release pattern, with lidocaine cleared from ointment within 4h (97.9% cumulative release), while cubosomal gels showed sustained release up to 24h (53.33-98.86% cumulative release). A skin retention study demonstrated that cubosomes can increase (up to 28-fold) the lidocaine content in the skin (4.56mg) compared to ointment (0.19mg). A rabbit skin irritation study showed no sign of irritation after the application of cubosomal gel. In the radiant heat tail-flick study, the local anesthetic effect of lidocaine from the cubosomal gel was sustained for up to 16h with 1.43-fold higher efficacy than marketed ointment. In conclusion, the study demonstrated the potential of cubosomal nanoparticle-laden gel to sustain the release of lidocaine for prolonging local anesthetic effects for pain management.