Laser-assisted delivery enhances topical uptake of the anticancer agent cisplatin

• Main Authors: Emily Wenande, Uffe H. Olesen, Malene R. Boesen, Daniel P. Persson, Catharina M. Lerche, Stefan Stürup, Bente Gammelgaard, Søren Husted, R. Rox Anderson, Merete Haedersdal
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-01-01
• Series: Drug Delivery
• Subjects: element bioimaging; fractional ablative co2 laser; laser-assisted drug delivery; local chemotherapy; non-melanoma skin cancer
• Online Access: http://dx.doi.org/10.1080/10717544.2018.1534896
• ISSN: 1071-7544; 1521-0464

Systemic chemotherapy with the anticancer agent cisplatin is approved for advanced non-melanoma skin cancer (NMSC), but topical treatment is limited by insufficient cutaneous penetration. We studied the impact of ablative fractional laser (AFL) exposure on topical cisplatin’s pharmacokinetics and biodistribution in skin, using microscopic ablation zones reaching the mid- (MAZ-MD; 620 μm depth) and deep dermis (MAZ-DD; 912 μm depth) (λ = 10,600 nm, 196 MAZ/cm2). Assessed in an in vitro Franz cell model after 0.5-, 4-, 24 h topical exposure (n = 8), cisplatin delivery was greatly accelerated by AFL, shown by quantitative- and imaging-based inductively coupled plasma-mass spectrometry (ICP-MS). After 30 minutes, cisplatin concentrations were 91.5, 90.8 and 37.8 μg/cm3 in specific 100-, 500, and 1500 μm skin layers respectively, contrasting to 8.08, 3.12, 0.64 μg/cm3 in non-laser-exposed control skin (p < .001; control vs MAZ-MD). Supported by element bioimaging, the greatest relative increases occurred in the deep skin compartment and at later time points. After 24 h, cisplatin concentrations thus rose to 1829, 1732 and 773 μg/cm3, representing a 25-, 103- and 447-fold enhancement in the 100, 500, and 1500 μm deep skin layers versus corresponding controls (p < .001; MAZ-MD). A significant difference in cutaneous uptake using MAZ-MD and MAZ-DD was not shown at any time point, though deeper laser channels resulted in increased transdermal cisplatin permeation (p ≤ .015). In conclusion, AFL is a rapid, practical and existing skin treatment that may provide greatly enhanced uptake of topical cisplatin for treatment of superficial and deep skin cancer.