Size-dependent penetration of nanoemulsions into epidermis and hair follicles: implications for transdermal delivery and immunization.

Rui Su,Zhongjian Chen,Ye Li,Qin Yu,Xiaochun Dong,Jianping Qi,Weili Zhao,Wufa Fan,Quangang Zhu,Yi Lu,Wei Wu

doi:10.18632/oncotarget.17130

Abstract

Nanoemulsions have been widely applied to dermal and transdermal drug delivery. However, whether and to what depth the integral nanoemulsions can permeate into the skin is not fully understood. In this study, an environment-responsive dye, P4, was loaded into nanoemulsions to track the transdermal translocation of the nanocarriers, while coumarin-6 was embedded to represent the cargoes. Particle size has great effects on the transdermal transportation of nanoemulsions. Integral nanoemulsions with particle size of 80 nm can diffuse into but not penetrate the viable epidermis. Instead, these nanoemulsions can efficiently fill the whole hair follicle canals and reach as deep as 588 μm underneath the dermal surfaces. The cargos are released from the nanoemulsions and diffuse into the surrounding dermal tissues. On the contrary, big nanoemulsions, with mean particle size of 500 nm, cannot penetrate the stratum corneum and can only migrate along the hair follicle canals. Nanoemulsions with median size, e.g. 200 nm, show moderate transdermal permeation effects among the three-size nanoemulsions. In addition, colocalization between nanoemulsions and immunofluorescence labeled antigen-presenting cells was observed in the epidermis and the hair follicles, implying possible capture of nanoemulsions by these cells. In conclusion, nanoemulsions are advantageous for transdermal delivery and potential in transcutaneous immunization.

Highlights

Skin is an attractive route for both local and systemic delivery of drugs [1,2,3,4]
Since it is accepted that particle size plays a key role in in vivo performance of nanoparticles, nanoemulsions with mean particle size of 80, 200 and 500 nm were prepared, respectively (Figure 1A, 1B and 1C)
As observed by Transmission electron microscopy (TEM), all of the nanoemulsions are spherical with smooth surfaces (Figure 1A, 1B and 1C)

Summary

INTRODUCTION

Skin is an attractive route for both local and systemic delivery of drugs [1,2,3,4]. the stratum corneum (SC), a ‘bricks and mortar’ structure, prevents entry of harmful xenobiotics as well as most therapeutic compounds into the body [5]. Others believe that the encapsulated drugs are released from the nanoemulsions and diffuse through the SC, while the compositions of nanoemulsions decreased the SC barriers by extracting the SC lipids as well as denaturing the proteins of keratinocytes [37,38,39] This difficult situation owes much to the lack of functional approaches to identify nanoparticles against the physiological background due to the small size of the nanocarriers. The distinct feature of these probes is the sensitive aggregation-caused quenching (ACQ) effects upon contact with water through π-π stacking These probes are highly hydrophobic and can be tightly embedded into either lipid or polymeric nanoparticles, where they emit intense fluorescence signals when being well dispersed. Specific attention is www.impactjournals.com/oncotarget paid to collect evidence on the translocation of integral nanoemulsions across the skin as well as the potential of ingestion of integral nanoemulsions by APCs in skin

RESULTS AND DISCUSSION

MATERIALS AND METHODS

CONFLICTS OF INTEREST