Methodological Research Paper:

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

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

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Oncotarget. 2017; 8:38214-38226. https://doi.org/10.18632/oncotarget.17130

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Rui Su1,2,3, Wufa Fan2, Qin Yu4, Xiaochun Dong2, Jianping Qi3,4, Quangang Zhu4, Weili Zhao2,4, Wei Wu2,4, Zhongjian Chen4, Ye Li3 and Yi Lu2,4

1 Shaanxi University of Chinese Medicine, Xianyang, P.R. China

2 School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai, P.R.China

3 Shaanxi Academy of Traditional Chinese Medicine, Xi’an, P.R. China

4 Shanghai Dermatology Hospital, Shanghai, P.R. China

Correspondence to:

Zhongjian Chen, email:

Ye Li, email:

Yi Lu, email:

Keywords: nanoemulsions, transdermal delivery, immunization, aggregation-caused quenching fluorescence, particle size

Received: February 21, 2017 Accepted: March 31, 2017 Published: April 16, 2017


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.

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