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 (103–227 nm), 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 4 h (97.9% cumulative release), while cubosomal gels showed sustained release up to 24 h (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 (4.56 mg) compared to ointment (0.19 mg). 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 16 h 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.

SCALP Block Model in Sprague-Dawley Rats; In Vivo Experimental Study and Model Identification

“…There are similar studies in the literature which used sedation and muscle relaxants (11)(12)(13)(14)(15). On the other hand, some studies used local anesthesia in line with ours (16)(17)(18)(19).…”

Design of Liposomal Lidocaine/Cannabidiol Fixed Combinations for Local Neuropathic Pain Treatment

“…The permeation of LD has been deeply investigated, and lipid-based carriers have been tested with the aim of prolonging the duration of action and the analgesic effect rather than improving skin permeation [6,7]. Conversely, the poor skin permeation data available for CBD indicate that the crossing through the skin of this compound is limited by its high hydrophobicity and affinity for stratum corneum components.…”

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain

“…Nevertheless, in a comprehensive literature review, the use of intravenous lidocaine infusion as a treatment for peripheral neuropathy was investigated, showing its effectiveness as a treatment option with minimal side effects [ 84 ]. Lidocaine can also be used in the form of sustained-release capsules, transmucosal patches, or oral gels/suspensions to exert longer lasting pain relief in cases of chronic or neuropathic pain [ 88 , 89 , 90 , 91 , 92 ].…”