Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin

Wenande, Emily; Tam, Joshua; Bhayana, Brijesh; Schlosser, Steven Kyle; Ishak, Emily; Farinelli, William A.; Chlopik, Agata; Hoang, Mai P.; Pinkhasov, Omar R.; Caravan, Peter; Anderson, R. Rox; Hædersdal, Merete

doi:10.1016/j.jconrel.2018.02.019

Cited by 32 publications

(38 citation statements)

References 44 publications

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“…good correlation with previous in vitro results (Olesen et al, 2019). In contrast, hydrophilic anticancer drugs cisplatin and 5-fluorouracil have displayed markedly lower concentrations in vivo than in vitro (Wenande et al, 2018a;Wenande et al, 2017;Wenande et al, 2018b). We speculate that vascular depletion of drug concentrations may be lower for hydrophobic molecules.…”

Section: Discussionsupporting

confidence: 88%

“…Skin integrity was tested using transepidermal water loss measurements with a Dermalab skin analyzer and transepidermal water loss probe (Cortex Technology, Hadsund, Denmark, n ¼ 2e4, averaged values shown). Clinical LSRs were documented using a Canon 750D with 60 mm macro lens and ring flash (Canon, Tokyo, Japan) and assessed independently by two evaluators (KH and KY) according to the OECD test scale (Draize scale) as previously described (Wenande et al, 2018b), scoring erythema on a scale of 0e4 and edema on a scale of 0e4. The combined score (0e8) was averaged for the two evaluators.…”

Section: Tolerability Assessmentmentioning

confidence: 99%

“…Ablative fractional lasers (AFLs) have been shown to enhance topical uptake of various drugs throughout the dermal layers by penetrating the skin in a grid of discrete microchannels, increasing clinical efficacy in treatment of skin malignancies (Choi et al, 2015;Haedersdal et al, 2014;Lee et al, 2011;Togsverd-Bo et al, 2015;Wenande et al, 2018b). Recently, substantially enhanced skin uptake of vismodegib has been shown in vitro and achieving concentrations well above previously reported plasma concentrations for oral vismodegib administration (Olesen et al, 2019).…”

Section: Introductionmentioning

confidence: 97%

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Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation

Olesen

Clergeaud

Hendel

et al. 2020

Journal of Investigative Dermatology

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Section: Discussionsupporting

confidence: 88%

Section: Tolerability Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation

Olesen

Clergeaud

Hendel

et al. 2020

Journal of Investigative Dermatology

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“…Early toxicological studies describe cisplatin as a mild skin irritant following 24-h topical exposure (INCHEM, 1991 ). Using the same 1 mg/mL cisplatin solution as applied here, normal appearances of in vivo porcine and murine skin are reported after simple topical application for 1–12 h (Miatmoko et al., 2015 , Wenande et al., 2018 ). Delivered by AFL however, the agent’s safety profile differs due enhanced skin uptake.…”

Section: Discussionmentioning

confidence: 99%

“…After 60 mins topical AFL-assisted cisplatin, increased erythema scores were observed over 5 days versus AFL alone. Meanwhile, cisplatin remained undetectable in plasma measured from 0–120 hours, despite >100 cm 2 skin exposures (Wenande et al., 2018 ). Though additional studies are needed, risks of AFL-assisted cisplatin therapy thus far appear acceptable.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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Propolis Enhances 5‐Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

Kocyigit,

Guler,

Durmus

et al. 2023

Chemistry & Biodiversity

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In this study, we investigated the combined treatment of 5‐fluorouracil (5‐FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase‐transfected (Lovo‐Luc CRC) cells and healthy colon cells (CCD‐18Co) to varying concentrations of 5‐FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti‐tumor effects of PE and 5‐FU using various methods. Our findings showed that the combination of PE and 5‐FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti‐tumor effectiveness of 5‐FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5‐FU through iROS generation in a dose‐dependent manner.

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Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin

Cited by 32 publications

References 44 publications

Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation

Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation

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

Propolis Enhances 5‐Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

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