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Germacrone and sesquiterpene-enriched extracts from Curcuma aeruginosa Roxb. increase skin penetration of minoxidil, a hair growth promoter

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Abstract

Minoxidil is approved for topical treatment of androgenic alopecia but hampered by poor cutaneous absorption. Recently, the randomized control trial showed that hair loss treatment of minoxidil was improved by co-application of the anti-androgen, Curcuma aeruginosa Roxb. extract. Here, we aimed to show that the apparent synergism arises from improved cutaneous penetration of minoxidil by bioactive compound, germacrone or C. aeruginosa (as an n-hexane extract, or essential oil). The partition coefficient of germacrone was determined by HPLC. Skin penetration was measured ex vivo on Franz diffusion cells using full thickness human foreskin as membranes. The receiver solution was sampled hourly for 8 h after which the skin was removed, the stratum corneum separated, and minoxidil assayed in this and in the remaining viable skin layer by HPLC. Skin penetration of minoxidil with 0.2 and 2% extract was increased ~ 4-fold (accumulated amount in receiver + skin viable layer after 8 h). Furthermore, germacrone enhanced minoxidil flux by ~ 10-fold and C. aeruginosa essential oil by ~ 20-fold. This work suggests three clinical consequences: (i) minoxidil efficacy is promoted, (ii) lower doses of minoxidil suffice, and (iii) C. aeruginosa extract/essential oil or germacrone can supplement treatment outcomes by acting as anti-androgen, thereby introducing a more effective topical treatment strategy for androgenic alopecia.

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Abbreviations

CA-ext:

Curcuma aeruginosa hexane extract

CA-oil:

Curcuma aeruginosa essential oil

ERsol:

solubility enhancement ratio

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Acknowledgements

We thank Dr. C. Norman Scholfield, Faculty of Pharmaceutical Sciences, Naresuan University for his help in the manuscript preparation. Dr. Wudticha Wisutriport, Ms. Prattana Khehaluna, Ms. Matusorn Wong-ona, and Ms. Ratchaprapa Sinlapasakkajohna are thanked for their help in the preliminary study.

Funding

The authors are grateful for the financial supports received from the Royal Golden Jubilee Program (RGJ-Ph.D., grant no. PHD/0205/2556), the Thailand Research Fund (the grant nos. DBG608005 and IRN58W0005), the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Office of the Higher Education Commission, Ministry of Education, and Naresuan University, Thailand.

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Correspondence to Kornkanok Ingkaninan.

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The investigational protocol was approved by Naresuan University Institutional Review Board (Approval No. HE-55-Ex-0134).

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The authors declare that there are no conflicts of interest.

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Srivilai, J., Waranuch, N., Tangsumranjit, A. et al. Germacrone and sesquiterpene-enriched extracts from Curcuma aeruginosa Roxb. increase skin penetration of minoxidil, a hair growth promoter. Drug Deliv. and Transl. Res. 8, 140–149 (2018). https://doi.org/10.1007/s13346-017-0447-7

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