Improve Transdermal Delivery Of Lidocaine Hydrochloride Using Elastic Nano-liposomes And Microneedle Arrays

Lidocaine hydrochloride(LDH)is a widely-used local anesthesia,normally administrated via injection.Currently,its transdermal application is employed before the surgeries on skin tissue for birthmark and tattoo removal,and before injections to kids.However,the transdermal formulations of local anesthesia still have long lag-time and low bio-availability.The stratum corneum of the skin is the major protective barrier of the body against the environment,hence also the main obstacle for transdermal drug delivery.Previous studies indicate that microneedle array(MN)can pierce the skin painlessly and generate micro-channels;and drug-loaded elastic liposomes can pass through pores smaller than their diameter and lower the surface tension in the skin.Both approaches enhance delivery efficiency significantly.Therefore,in this study,elastic liposomal formulation as well as microneedle arrays are recruited in order to improve the transdermal delivery efficiency of LDH,shorten the lag-time and increase its bio-availability.Our experiments are composed of four main parts:First,preparation,characterization and optimization of LDH-loaded elastic liposome formulation;Second,determination of the loading efficiency of LDH in elastic liposomes,assessment of its cellular toxicity and pharmaceutical characterization of the formulations;Third,in vitro transfusion study of liposomal formulations on MN-pretreated skin;Fourth,in vivo pharmacodynamics study comparing EMLA and LDH-loaded elastic liposomes.(?)The elastic liposomes were prepared using reverse evaporation after comparing among several methods,and the parameters were optimized as followed:the mass ratio of soybean phosphatidylcholine to cholesterol was 5:1;pH at 8.0,using chloroform as the organic solvent.Cytotoxic studies have shown no toxic effect on co-cultured human keratinocytes.The Span 80-and Tween 80-containing liposomal formulations applied on MN-pretreated skin have showed 1.86 and 2.4 times higher flux than those on the intact skin,and 2.47 and 3.11 times higher than those of LDH solution applied on intact skin,respectively in in vitro transfusion experiments.Application of EMLA on the MN-pretreatment of the skin resulted in much longer time under anesthesia.When applying LDH-loaded elastic liposomes,the local skin tissue can be anesthetized up to one hour,compared to 20 min in the control group using LDH solution.The results show that the combination of MN and elastic liposomes an effective approach to improve the transdermal drug delivery,which can significantly shorten the lag-time of tropical lidocaine application,prolong the time under anesthesia and increase the bio-availability of LDH,therefore help pain relief of the patients.This strategy is of potent application value and can be employed to enhance the transdermal delivery of other hydrophilic small molecule drugs.