Enhanced Iontophoretic Delivery of Magnesium Ascorbyl 2-Phosphate and Sodium Fluorescein to Hairless and Hairy Mouse Skin

Abstract

We recently reported that L-ascorbic acid 2-phosphate (AP) stimulates the growth of human dermal papilla (DP) cells, induces secretion of IGF-1 from the DP cells to promote hair shafts elongation in cultured human hair follicles, and triggers early progression from the telogen to anagen phase in mice. Since the magnesium salt of AP (APMg) is a highly hydrophilic ionic molecule, it is not easy to deliver this reagent to the skin or hair follicles by topical application alone. In order to enhance skin penetration of APMg without changing any molecular properties, a non-invasive iontophoretic delivery method was introduced. Iontophoresis of the negatively charged APMg under the electrode bearing same charge (cathode) significantly enhanced the in vitro penetration of APMg into a Franz cell equipped with mouse dorsal skin. In contrast, iontophoretic movement with the anode inhibited APMg penetration achieved with passive diffusion alone. The effect of iontophoresis on enhancing the penetration of APMg was also found to be much higher in the skin of hairy mice (3 - 8 times) compared to hairless mice (1.5 - 2.5 times). These findings indicated that iontophoretic movement induced the transfollicular pathway more strongly and effectively than the transdermal pathway. This phenomena was also demonstrated by the in vivo iontophoretic delivery of sodium fluorescein using hairy and hairless mice. The degree of iontophoretic enhancement during APMg penetration was also dependent on various conditions such as current density and application duration.

Share and Cite:

M. Kang, S. Kim, Y. Sung, M. Kim, J. Kim and I. Han, "Enhanced Iontophoretic Delivery of Magnesium Ascorbyl 2-Phosphate and Sodium Fluorescein to Hairless and Hairy Mouse Skin," Journal of Cosmetics, Dermatological Sciences and Applications, Vol. 2 No. 4, 2012, pp. 283-287. doi: 10.4236/jcdsa.2012.24054.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] R. Paus, S. Muller-Rover, C. Van Der Veen, et al., “A Comprehensive Guide for the Recognition and Classification of Distinct Stages of Hair Follicle Morphogenesis,” Journal of Investigative Dermatology, Vol. 113, No. 4, 1999, pp. 523-532. doi:10.1046/j.1523-1747.1999.00740.x
[2] S. Takamizawa, Y. Maehata, K. Imai, et al., “Effects of Ascorbic Acid and Ascorbic Acid 2-Phosphate, a Long-Acting Vitamin C Derivative, on the Proliferation and Differentiate on of Human Osteoblast-Like Cells,” Cell Biology International, Vol. 28, No. 4, 2004, pp. 255-265. doi:10.1016/j.cellbi.2004.01.010
[3] M. H. Kwack, S. H. Shin, S. R. Kim, et al., “L-Ascorbic Acid 2-Phosphate Promotes Elongation of Hair Shafts via the Secretion of Insulin-Like Growth Factor-1 from Dermal Papilla Cells through Phosphatidylinositol 3-Kinase. British Journal of Dermatology, Vol. 160, No. 6, 2009, pp. 1157-1162. doi:10.1111/j.1365-2133.2009.09108.x
[4] Y. K. Sung, S. Y. Hwang, S. Y. Cha, et al., “The Hair Growth Promoting Effect of Ascorbic Acid 2-Phosphate, a Long-Acting Vitamin C Derivative,” Journal of Dermatological Science, Vol. 41, No. 2, 2006, pp. 150-152. doi:10.1016/j.jdermsci.2005.11.010
[5] Y. K. Sung, M. H. Kwack, S. R. Kim, et al., “Transcriptional Activation of CCN1 and CCN2, Targets of Canonical Wnt Signal, by Ascorbic Acid 2-Phosphate in Human Dermal Papilla Cells,” Journal of Dermatological Science, Vol. 49, No. 3, 2009, pp. 256-259. doi:10.1016/j.jdermsci.2007.09.005
[6] F. Marra, J. Levy, P. Santi and Y. Kalia, “In Vitro Evaluation of the Effect of Electrotreatment on Skin Permeability,” Journal of Cosmetic Dermatology, Vol. 7, No. 2, 2008, pp. 105-111. doi:10.1111/j.1473-2165.2008.00372.x
[7] J. Yoo, S. Shanmugam, C. Song, et al., “Skin Penetration and Retention of L-Ascorbic Acid 2-Phosphate Using Mutilamellar Vesicles,” Archives of Pharmacal Research, Vol. 31, No. 12, 2008, pp. 1652-1658. doi:10.1007/s12272-001-2164-4
[8] M. Ebihara, M. Akiyama, Y. Ohnishi, et al., “Iontophoresis Promotes Percutaneous Absorption of L-Ascorbic Acid in Rat Skin,” Journal of Dermatological Science, Vol. 32, No. 3, 2003, pp. 217-222. doi:10.1016/S0923-1811(03)00105-1
[9] I. Han, M. Kim and J. Kim, “Enhanced Transfollicular Delivery of Adriamycin with a Liposome and Iontophoresis,” Experimental Dermatology, Vol. 13, No. 2, 2004, pp. 86-92. doi:10.1111/j.0906-6705.2004.00123.x
[10] K. Kajimoto, M. Yamamoto, M. Watanabe, et al., “Non-invasive and Persistent Transfollicular Delivery System Using a Combination of Liposomes and Iontophoresis,” International Journal of Pharmaceutics, Vol. 403, No. 1-2, 2011, pp. 57-65. doi:10.1016/j.ijpharm.2010.10.021
[11] E. R. Scott, A. I. Laplaza, H. S. White and J. B. Phipps, “Transport of Ionic Species in Skin: Contribution of Pores to the Overall Skin Conductance,” Pharmaceutical Research, Vol. 10, No. 12, 1993, pp. 1699-1709. doi:10.1023/A:1018909811672
[12] B. D. Bath, E. R. Scott, P. Bradley and H. S. White, “Scanning Electrochemical Microscopy of Iontophoretic Transport in Hairless Mouse Skin. Analysis of the relative Contributions of Diffusion, Migration, and Electroosmosis to Transport in Hair Follicles,” Journal of Dermatological Science, Vol. 89, No. 12, 2000, pp. 1537-1549. doi:10.1002/1520-6017(200012)89:12<1537::AID-JPS4>3.0.CO;2-J
[13] P. Minhas, V. Bansal, J. Patel, et al., “Electrodes for High-Definition Transcutaneous DC Stimulation for Applications in Drug Delivery and Electrotherapy, Including tDCS,” Journal of Neuroscience Methods, Vol. 190, No. 2, 2000, pp. 188-197. doi:10.1016/j.jneumeth.2010.05.007

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.