Topical delivery of vismodegib using ablative fractional laser and micro-emulsion formulation in vitro

Lasers in Surgery and Medicine
Uffe H OlesenMerete Haedersdal

Abstract

Hedgehog inhibitors such as vismodegib are targeted drugs widely used for the treatment of basal cell carcinomas; however, their use is significantly limited by frequent systemic side effects due to oral administration route. We aim to use ablative fractional laser (AFL) to enable the topical delivery of vismodegib to relevant dermal depths. Pig skin was treated in vitro with a fractional 10,600 nm CO2 laser at 0 or 80 mJ/microbeam and exposed to vismodegib (6.4 mmol/L) in Franz-diffusion cells for 0.5, 4, and 24 hours (n = 54 samples), either formulated in a micro-emulsion composed of soybean oil and Tween 80 or dissolved in ethanol as vehicle control. Vismodegib biodistribution was studied at specific skin depths from 0 to 1,800 µm (incremental steps of 300 µm) by mass spectrometry. Combination of AFL and vismodegib emulsion substantially enhanced the delivery of drug into the skin. Emulsion formulation alone yielded higher vismodegib skin concentrations compared to vehicle control in superficial and mid-dermis (0-900 µm, P = 0.002-0.015). The over-all highest concentration found (554.5 µmol/L) was reached at 24 hours in superficial (0-300 µm) AFL exposed skin, 7.6-fold higher than vehicle control (P = 0.002) and 9.7-101.6 fo...Continue Reading

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Citations

Dec 19, 2018·Lasers in Surgery and Medicine·Kristen M Kelly
Mar 26, 2019·Lasers in Surgery and Medicine·Arne A MeestersAlbert Wolkerstorfer
Aug 8, 2019·Expert Opinion on Drug Delivery·Chien-Yu HsiaoJia-You Fang
Feb 13, 2020·Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]·Jusleen AhluwaliaArisa E Ortiz
Oct 1, 2020·Lasers in Surgery and Medicine·Rikke L ChristensenUffe H Olesen
Nov 28, 2019·Current Treatment Options in Oncology·Erica LeavittStephanie Martin

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