Drug penetration enhancement techniques in ablative fractional laser assisted cutaneous delivery of indocyanine green

Meesters, Arne A.; Nieboer, Marilin J.; Almasian, Mitra; Georgiou, Giota; Rie, Menno A. de; Verdaasdonk, Rudolf M.; Wolkerstorfer, Albert

doi:10.1002/lsm.23088

Cited by 9 publications

(7 citation statements)

References 31 publications

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“…As stated in our previous study [10], only depths of up to 400 μm are investigated. Therefore, no conclusions can be drawn regarding the deposition of ICG in deeper skin layers.…”

Section: Discussionmentioning

confidence: 99%

“…Since virtually all topical drugs that are commercially available are optimized for application on the intact skin, providing gradual release of the active substance through the stratum corneum, the development of new drug formulations exclusively for the purpose of fractional laser-assisted (or microneedling assisted) drug delivery is mandatory for the successful clinical application of this technique. In addition, physical penetration enhancement techniques, such as massage or ultrasound techniques, may be used to further enhance topical drug delivery in clinical practice [10].…”

Section: Discussionmentioning

confidence: 99%

“…As skin samples were anonymized, a formal review procedure of the protocol by the Medical Ethics Committee was not required. Skin samples were stored and prepared according to a standardized protocol published earlier [10].…”

Section: Skin Samplesmentioning

confidence: 99%

“…ICG is a hydrophilic drug (Log P − 0.29) with a molecular weight of 775 Da. ICG was diluted with demineralized water to a concentration of 0.08 mg/ml according to the protocol published in our earlier study [10].…”

Section: Indocyanine Greenmentioning

confidence: 99%

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Enhanced topical cutaneous delivery of indocyanine green after various pretreatment regimens: comparison of fractional CO2 laser, fractional Er:YAG laser, microneedling, and radiofrequency

et al. 2020

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Different devices have been used to enhance topical drug delivery. Aim of this study was to compare the efficacy of different skin pretreatment regimens in topical drug delivery. In six ex vivo human abdominal skin samples, test regions were pretreated with fractional CO 2 and Er:YAG laser (both 70 and 300 μm ablation depth, density of 5%), microneedling (500 μm needle length), fractional radiofrequency (ablation depth of ± 80-90 μm), and no pretreatment. The fluorescent agent indocyanine green (ICG) was applied. After 3 h, fluorescence intensity was measured at several depths using fluorescence photography. Significantly higher surface fluorescence intensities were found for pretreatment with fractional Er:YAG and CO 2 laser and for microneedling vs. no pretreatment (p < 0.05), but not for radiofrequency vs. no pretreatment (p = 0.173). Fluorescence intensity was highest for the Er:YAG laser with 300 μm ablation depth (mean 38.89 arbitrary units; AU), followed by microneedling (33.02 AU) and CO 2 laser with 300 μm ablation depth (26.25 AU). Pretreatment with both lasers with 300 μm ablation depth gave higher fluorescence intensity than with 70 μm ablation depth (Er:YAG laser, 21.65; CO 2 laser, 18.50 AU). Mean fluorescence intensity for radiofrequency was 15.27 AU. Results were comparable at 200 and 400 μm depth in the skin. Pretreatment of the skin with fractional CO 2 laser, fractional Er:YAG laser, and microneedling is effective for topical ICG delivery, while fractional radiofrequency is not. Deeper laser ablation results in improved ICG delivery. These findings may be relevant for the delivery of other drugs with comparable molecular properties.

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“…As stated in our previous study [10], only depths of up to 400 μm are investigated. Therefore, no conclusions can be drawn regarding the deposition of ICG in deeper skin layers.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Skin Samplesmentioning

confidence: 99%

Section: Indocyanine Greenmentioning

confidence: 99%

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Enhanced topical cutaneous delivery of indocyanine green after various pretreatment regimens: comparison of fractional CO2 laser, fractional Er:YAG laser, microneedling, and radiofrequency

et al. 2020

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“…We routinely topically apply or intralesionally inject Kenacort A40 immediately following treatment with the CO 2 ‐AFL. Laser‐assisted delivery of drugs is an evolving technique , enhancing the bioavailability of topically applied drugs, and the positive effects of corticosteroids on burn scars are well known . Thus, to what extent this treatment influenced our results remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Ablative fractional resurfacing with laser‐facilitated steroid delivery for burn scar management: Does the depth of laser penetration matter?

et al. 2019

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Background and Objective To investigate whether the depth of ablative fractional CO2 laser (CO2‐AFL) penetration of pathological burn scars influences clinical outcomes. Study Design/Materials and Methods All patients presenting to the Concord Repatriation General Hospital (CRGH) Scar Clinic received ultrasound measurement at the thickest point of their burn scars. Subsequently, the effect of various CO2‐AFL settings (energy which correlates to penetration depths) on different outcome parameters was analysed. Patients were divided into five groups depending on minimal scar penetration depth. Results Seventy‐eight patients (158 scars) had complete data allowing for analysis. Median scar thickness was 3,400 μm and median laser scar penetration depth was 900 μm. Scar penetration categories were as follows: 0–25% (n = 40), 25–50% (n = 67), 50–75% (n = 31), 75–100% (n = 8), >100% (n = 3) of scar thickness. The median reduction in maximum scar thickness was 800 μm following one treatment (P < 0.001). However, this effect depended on scar penetration depth, whereby scars that were penetrated ≥75% showed no significant improvement in scar thickness and those penetrated >100% indicated a tendency to become worse. Other assessed outcome parameters included: the Vancouver Scar Scale, the Patient and Observer Scar Assessment Scale, a neuropathic pain score (DN4 Pain Questionnaire), and a pruritus score (modified D4 Pruritus Score). All these factors showed significant improvement in the categories up to 75% scar penetration depth. Conclusions CO2‐AFL scar penetration depth significantly influences subjective and objective pathologic burn scar modulation. The penetration depth of 51–75% achieves the greatest reduction in scar thickness. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

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Topical delivery of PD‐1 inhibitors with laser‐assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns

et al. 2021

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Background and Objectives: Current cancer immunotherapeutic treatment with PD-1 inhibitors is administered systemically. However, a local treatment strategy may be advantageous as it could provide targeted drug delivery as well as attenuate side effects seen with systemic treatments. For keratinocyte cancers, where surgical excision is not always applicable, an alternate local treatment approach would be beneficial. This study aims to examine cutaneous pharmacokinetics and biodistribution of the PD-1 inhibitor nivolumab, locally delivered either by ablative fractional laser (AFL)-assisted passive diffusion or active intradermal injection, in vivo. Materials and Methods: In vivo pig skin was either exposed to CO 2 AFL (80 mJ/ mb by two stacked pulses of 40 mJ/mb) at 5% or 15% density followed by topical application of nivolumab (1 mg/ml, 100 µl/10 × 10 mm) or intradermally injected with nivolumab (1 mg/ml, 100 µl). Cutaneous nivolumab delivery was evaluated at different timepoints (0, 1, 2, 4 hours and 2 days) at two tissue depths (100-800 and 900-1600 µm) by ELISA. Visualization of cutaneous biodistribution was shown in vertical tissue sections using HiLyte Fluor TM 488 SE labeled nivolumab for fluorescence microscopy whereas nivolumab was DOTA-tagged with Dysprosium before the laser ablation-inductively coupled plasma-mass spectrometry analysis (LA-ICP-MS). Results: Our in vivo study revealed different pharmacokinetic and biodistribution patterns for the AFL-and injection techniques. A superficial horizontal band-like uptake of nivolumab was provided with AFL-assisted passive diffusion whereas a deep focal deposition was seen with active intradermal injection, compared with controls showing remnant deposition on the skin surface. AFL-assisted nivolumab uptake in upper dermis peaked after 4 hours (p < 0.01). The cutaneous concentration of nivolumab achieved by intradermal injection was markedly higher than with AFL, the highest deposition with intradermal injection was detected at time 0 hours in both upper and deep dermis (p < 0.01) and decreased throughout the study period, although the concentration remained higher compared with saline control injections at all time points (0 hours -2 d) (p < 0.01). Conclusion:Local cutaneous delivery of nivolumab with either AFL or intradermal injection revealed two different pharmacokinetic and biodistribution patterns. Passive AFL-assisted diffusion of nivolumab resulted in enhanced uptake after 4 hours, while intradermal actively injected nivolumab showed immediate enhanced cutaneous deposition with retention up to 2 days after

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Drug penetration enhancement techniques in ablative fractional laser assisted cutaneous delivery of indocyanine green

Cited by 9 publications

References 31 publications

Enhanced topical cutaneous delivery of indocyanine green after various pretreatment regimens: comparison of fractional CO2 laser, fractional Er:YAG laser, microneedling, and radiofrequency

Enhanced topical cutaneous delivery of indocyanine green after various pretreatment regimens: comparison of fractional CO2 laser, fractional Er:YAG laser, microneedling, and radiofrequency

Ablative fractional resurfacing with laser‐facilitated steroid delivery for burn scar management: Does the depth of laser penetration matter?

Topical delivery of PD‐1 inhibitors with laser‐assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns

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