Penetration pathways induced by low-frequency sonophoresis with physical and chemical enhancers: iron oxide nanoparticles versus lanthanum nitrates.
Low-frequency sonophoresis (LFS) has been shown to disrupt the structure of stratum corneum (SC) lipid bilayers and enhance SC permeability. In this study, we examined the penetration pathway of lanthanum nitrate (LaNO(3)) tracer in viable epidermis after combined treatment of LFS and tape stripping (TS), as a physical enhancer, or oleic acid (OA) application, as a chemical enhancer, using transmission electron microscopy (TEM). As a positive control, we visualized the passive diffusion pathway of LaNO(3) and iron oxide (Fe(3)O(4)) nanoparticles after the incision of hairless mouse skin. Next, we applied LFS immediately after TS or OA application and visualized the penetration pathway of LaNO(3). Each treatment showed restricted penetration to the SC-stratum granulosum (SG) interface or upper SG layer. However, the additional application of LFS induced diffuse intracellular distribution of LaNO(3) throughout the viable epidermis. Quantitative analysis also revealed that combined treatment significantly increases LaNO(3) penetration into viable epidermis when compared with each treatment. Our ultrastructural findings show the synergistic effect of LFS and TS or OA application on transdermal drug delivery. We also found that this combined treatment enhances the penetration of LaNO(3) through the viable epidermis through an intracellular pathway.
Lee
Sang Eun
SE
Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. ydshderm@yuhs.ac
Choi
Ki Ju
KJ
Menon
Gopinathan K
GK
Kim
Hyun Jung
HJ
Choi
Eung Ho
EH
Ahn
Sung Ku
SK
Lee
Seung Hun
SH
D000279:Administration, Cutaneous; D000818:Animals; D004058:Diffusion; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004817:Epidermis / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007811:Lanthanum / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D019301:Oleic Acid / Q000493:pharmacokinetics; D014465:Ultrasonics
D005290:Ferric Compounds; C000499:ferric oxide; D019301:Oleic Acid; C016534:lanthanide nitrate; D007811:Lanthanum