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.

Feasibility of using optical coherence tomography to detect radiation-induced fibrosis and residual cancer extent after neoadjuvant chemo-radiation therapy: an ex vivo study.

Treatment of resectable esophageal cancer includes neoadjuvant chemo-radiation therapy (nCRT) followed by esophagectomy in operable patients. High-risk surgery may have been avoided in patients with a pathological complete response (pCR). We investigated the feasibility of optical coherence tomography (OCT) to detect residual cancer and radiation-induced fibrosis in 10 esophageal cancer patients that underwent nCRT followed by esophagectomy. We compared our OCT findings with histopathology. Overall, OCT was able to differentiate between healthy tissue, fibrotic tissue, and residual cancer with a sensitivity and specificity of 79% and 67%, respectively. Hence, OCT has the potential to add to the assessment of a pCR.