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Microneedle-Mediated Delivery of Copper Peptide Through Skin

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ABSTRACT

Purpose

Copper peptide (GHK-Cu) plays an important role in skin regeneration and wound healing. However, its skin absorption remains challenging due to its hydrophilicity. Here we use polymeric microneedle array to pre-treat skin to enhance GHK-Cu skin penetration.

Methods

Two in vitro skin models were used to assess the capability of microneedles in facilitating skin delivery of GHK-Cu. Histological assay and confocal laser scanning microscopy were performed to characterize and quantify the microconduits created by the microneedles inside skin. Cellular and porcine models were used to evaluate the safety of microneedle-assisted copper peptide delivery.

Results

The depth and percentage of microneedle penetration were correlated with application forces, which in turn influenced the extent of enhancement in the skin permeability of GHK-Cu. In 9 h, 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated though the microneedle treated human skin, while almost no peptide or copper permeated through intact human skin. No obvious signs of skin irritation were observed with the use of GHK-Cu after microneedle pretreatment.

Conclusions

It is effective and safe to enhance the skin permeation of GHK-Cu by using microneedles. This approach may be useful to deliver similar peptides or minerals through skin.

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Abbreviations

AAS:

Atomic absorption spectroscopy

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

GHK:

Glycyl-L-histidyl-L-lysyl

GHK-Cu:

Copper peptide

HaCaT:

Human adult low calcium high temperature

HDF:

Human dermal fibroblasts

HPLC:

High performance liquid chromatography

MN:

Microneedle

MSS:

Microchannel Skin System

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

PBS:

Phosphate buffered saline

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ACKNOWLEDGMENTS AND DISCLOSURES

The study is supported by a Singapore EDB-IPP grant (grant number: RL2012-035). We thank Siew Ping Yeo from 3M Innovation Singapore for helping with the scanning electron microscopy imaging.

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Authors and Affiliations

  1. Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore, Singapore, 117543

    Hairui Li, Yong Sheng Jason Low, Hui Ping Chong & Lifeng Kang

  2. 3M Innovation Singapore, 100 Woodlands Avenue, Singapore, Singapore, 738205

    Hairui Li, Melvin T. Zin, Chi-Ying Lee, Bo Li & Melvina Leolukman

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  1. Hairui Li
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Correspondence to Lifeng Kang.

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Li, H., Low, Y.S.J., Chong, H.P. et al. Microneedle-Mediated Delivery of Copper Peptide Through Skin. Pharm Res 32, 2678–2689 (2015). https://doi.org/10.1007/s11095-015-1652-z

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  • DOI: https://doi.org/10.1007/s11095-015-1652-z

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