Developing transcutaneous nanoenabled anaesthetics for eyelid surgery.

Abstract

Local anaesthesia in eyelid surgery carries inherent risks, which has spurned ongoing investigation to identify needleless alternatives. Nanomedicines (particles ranging between 10 nm and 1000 nm in size) have shown promise in the transcutaneous delivery of certain drugs. In this study, we explore the feasibility of nanoenabled lidocaine delivery across an artificial skin analogue. Three different lidocaine-loaded nanocarriers were characterised. Diffusion studies were performed through cellulose membranes using customised Franz cells. The nanocarriers included polymeric micelles (PMs) (Soluplus), solid lipid nanoparticles (SLNs) (Tripalmitin: Lecithin: Labrasol: polysorbate-20: water; 3.33:1:40:1:4.67 w/w) and self-nanoemulsifying drug delivery systems (SNEDDS) (Capryol-90: Transcutol: Labrasol; 1:3:6 w/w). Particles were characterised in terms of size, zeta-potential and morphology. One-way analysis of variance (ANOVA) with post hoc Tukey's tests were used to assess differences in permeation at a significance of p<0.05. Lidocaine loading was highest in SNEDDs (50±2.1 mg/g) compared with PMs (13.4±0.6 mg/mL) and SLNs (2.8±0.5 mg/mL). All particles possessed a size below 150 nm, illustrated good colloidal stability with a negative zeta-potential and a spherical morphology as demonstrated by transmission electron microscopy images. Cumulative lidocaine concentration after 6 h was significant for both PMs (345.7±23.8 µg/cm(2)/h) and SNEDDS (224.8±118.2 µg/cm(2)/h) compared with SLNs (127.3±25.4 µg/cm(2)/h). However, SLNs provided controlled release of lidocaine with a linear gradient that continued to increase up to 6 h. These results highlight the potential capability of nanoparticle lidocaine delivery in eyelid surgery. The achieved flux for all nanomedicines was higher than that reported for currently approved topical lidocaine formulations (including EMLA cream).