Feasibility of transdermal delivery of lidocaine-loaded nanocarriers through artificial and human skin: a pilot study

Background:There is a growing demand for painless, rapid onset, long duration anaesthesia in many aspects of medicine. Nanomedicines (particles 50–500 nm) have shown promise in topical delivery of certain drugs. In this study we explored the feasibility of transdermal delivery of lidocaine across artificial membranes and human skin.MethodsThree different nanocarriers were optimised and characterised for lidocaine loading. Permeation of lidocaine was performed with modified, individually calibrated Franz cells across cellulose membrane and eyelid skin. The nanocarriers were polymeric micelles, solid lipid nanoparticles, and self-nanoemulsifying drug delivery systems (SNEDDs) or nanoemulsion. One-way ANOVA with post-hoc Tukey test was used to assess differences in permeation.FindingsSNEDD showed the highest lidocaine loading and was the most stable of all nanomedicines. Transmission electron microscope images demonstrated translucency of all suspensions with spherical morphology, which coincided with the measured particle sizes (all <200 nm). The cumulative release of lidocaine-loaded SNEDDs (277 μg/cm2 per h) and polymeric micelles (193 μg/cm2 per h) were highest across cellulose membrane, and the flux through eyelid skin was the highest with lidocaine-loaded SNEDDs (143 μg/cm2 per h) and solid lipid nanoparticles (314 μg/cm2per h).InterpretationBecause of the lipid perturbation effects of human skin, the performance of the nanocarriers was altered compared with the artificial membrane, but overall the achieved flux for all nanomedicines was higher than that previously reported for topical anaesthetic cream tested in skin (73·81 μg/cm2per h for lidocaine hydrochloride and 53·93 μg/cm2 per h for prilocaine hydrochloride). We have highlighted the potential capability and use of this mode of drug delivery in eyelid surgery.FundingRoyal Society