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

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 CO2 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 CO2 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 CO2 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; CO2 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 CO2 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.

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

BACKGROUND AND OBJECTIVES: Topical drug delivery can be increased by pretreatment of the skin with ablative fractional laser (AFXL). Several physical penetration enhancement techniques have been investigated to further improve AFXL-assisted drug delivery. This study investigated the influence of three of these techniques, namely massage, acoustic pressure wave treatment, and pressure vacuum alterations (PVP) on the distribution of the fluorescent drug indocyanine green (ICG) at different depths in the skin after topical application on AFXL pretreated skin. MATERIALS AND METHODS: In ex vivo human skin, test regions were pretreated with AFXL (10,600 nm, channel depth 300 µm, channel width 120 µm, density 15%). Subsequently, ICG was applied, followed by massage, acoustic pressure wave treatment or PVP. ICG fluorescence intensity (FI) was assessed after 1, 3, and 24 hours at several depths using fluorescence photography. RESULTS: FI was higher when using enhancement techniques compared to control (AFXL-only) up to 3 hours application time (P < 0.05). After 3 hours, mean surface FI was highest after acoustic pressure wave treatment (61.5 arbitrary units; AU), followed by massage (57.5AU) and PVP (46.9AU), respectively (for comparison: AFXL-only 31.6AU, no pretreatment 14.9AU). Comparable or higher FI was achieved already after 1 hour with enhancement techniques compared to 3-24 hours application time without. After 24 hours, no significant differences between enhancement techniques and AFXL-only were observed (P = 0.31). CONCLUSION: Penetration enhancement techniques, especially acoustic pressure wave treatment and massage, result in improved drug accumulation in AFXL-pretreated skin and reduce the application time needed. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Parameters in fractional laser assisted delivery of topical anesthetics: Role of laser type and laser settings.

BACKGROUND AND OBJECTIVES: Efficacy of topical anesthetics can be enhanced by pretreatment of the skin with ablative fractional lasers. However, little is known about the role of parameters such as laser modality and laser density settings in this technique. Aims of this study were to compare the efficacy of pretreatment with two different ablative fractional laser modalities, a CO2 laser and an Er:YAG laser, and to assess the role of laser density in ablative fractional laser assisted topical anesthesia. STUDY DESIGN/MATERIALS AND METHODS: In each of 15 healthy subjects, four 10 × 10 mm test regions on the back were randomized to pretreatment (70-75 µm ablation depth) with CO2 laser at 5% density, CO2 laser at 15% density, Er:YAG laser at 5% density or Er:YAG laser at 15% density. Articaine hydrochloride 40 mg/ml + epinephrine 10 µg/ml solution was applied under occlusion to all four test regions. After 15 minutes, a pass with the CO2 laser (1,500 µm ablation depth) was administered as pain stimulus to each test region. A reference pain stimulus was given on unanesthetized skin. The main outcome parameter, pain, was scored on a 0-10 visual analogue scale (VAS) after each pain stimulus. RESULTS: Median VAS scores were 1.50 [CO2 5%], 0.50 [CO2 15%], 1.50 [Er:YAG 5%], 0.43 [Er:YAG 15%], and 4.50 [unanesthetized reference]. VAS scores for all pretreated test regions were significantly lower compared to the untreated reference region (P < 0.01). We found no significant difference in VAS scores between the CO2 and the Er:YAG laser pretreated regions. However, VAS scores were significantly lower at 15% density compared to 5% density for both for the CO2 laser (P < 0.05) and the Er:YAG laser (P < 0.01). Pretreatment with the CO2 laser was considered slightly more painful than pretreatment with Er:YAG laser by the subjects. CONCLUSION: Fractional laser assisted topical anesthesia is effective even with very low energy settings and an occlusion time of only 15 minutes. Both the CO2 laser and the Er:YAG laser can be used to assist topical anesthesia although the CO2 laser pretreatment is experienced as more painful. In our study settings, using articaine/epinephrine solution and an occlusion time of 15 minutes, a density of 15% was more effective than 5%. Lasers Surg. Med. 50:813-818, 2018. © 2018 Wiley Periodicals, Inc.