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Abstract Title:

Topical delivery of gambogic acid assisted by the combination of low-frequency ultrasound and chemical enhancers for chemotherapy of cutaneous melanoma.

Abstract Source:

Eur J Pharm Sci. 2021 Aug 12 ;166:105975. Epub 2021 Aug 12. PMID: 34391880

Abstract Author(s):

Ding Zhang, Boqi Chen, Qingke Mu, Wei Wang, Kaili Liang, Liyan Wang, Qing Wang

Article Affiliation:

Ding Zhang

Abstract:

Anti-cutaneous melanoma activity of the skin-delivered gambogic acid (GA) has been reported in our previous study. However, it is difficult for GA to diffuse passively through intact skin without any enhancement means. In this study, a combination of chemical enhancers (EN: azone and propylene glycol) and physical ultrasound (US) was used to improve the percutaneous permeation of GA and enhance the anti-melanoma activity. The enhancement effect of the combination of EN and US (EN-US) on GA in vitro and in vivo was studied, and the enhancement mechanism and skin irritation were also evaluated. We showed that the parameters of US application at a constant frequency (30 kHz) with a duty cycle of 100% and intensity of 1.75 W/cmfor 20 min were optimal. In vitro, EN-US showed a considerable enhancement of the permeation of GA, and the enhancement effect was stronger than that with the use of EN or US alone. In vivo antitumor study showed that the tumor growth was significantly inhibited after percutaneous administration of GA byEN-US, more than in the intravenous injection group. The penetration enhancement mechanism revealed that EN-US not only altered the structure of lipid bilayers and keratins to reduce the barrier effect of the stratum corneum but also produced diffusion channels in the skin under the cavitation effect of US, thereby promoting the skin penetration of GA. In addition, there was no observable skin irritation in mice after treatment with EN-US. Our study demonstrated that the combination of EN and US improved the skin permeation and retention of GA to enhance the anti-melanoma activity. This method also provides technical guidance for the future development of topical and transdermal therapeutic system of GA.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Chemotherapeutic : CK(2328) : AC(1086)

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