Transdermal delivery of water‐soluble fluorescent antibody mediated by fractional Er:YAG laser for the diagnosis of lupus erythematosus in mice

Abstract

Objectives Although transdermal drug delivery system (TDDS) has been successfully used for delivering small molecules, its application in the delivery of diagnostic antibodies has been limited due to their large size. In this study, we aim to obtain a broad insight in the dynamics of TRITC‐conjugated Goat Anti‐Mouse IgG (T‐IgG) uptake in fractional Er:YAG laser pretreated skin and provide a new technical option for detecting lupus erythematosus (LE) in mice. Methods The skins of SD and MRL/lpr mice were treated by fractional Er:YAG laser followed by external application of T‐IgG. The classic Franz diffusion method was used to observe the effects of different fractional fluences, densities and antibody concentrations on transdermal delivery of T‐IgG at different time points (2, 4, 6, 8, 20, and 24 hours). Frozen tissue sections and confocal microscopy were used to observe the distribution of T‐IgG on the sagittal and coronal planes of murine skin. Results Increased laser fluence (12.5 J/cm2 to 37.5 J/cm2) within 24 hours resulted in the obvious increase in transdermal amounts of T‐IgG during the early stage (before 8 hours). However, increasing laser density (100 pores/cm2 to 200 pores/cm2) produced a significant increase in T‐IgG permeation during the late stage (20 and 24 hours). Unlike fluence and density, increase in T‐IgG loading concentration (0.5 to 2 μg/μl) led to continuous increase in the whole process of transdermal delivery. T‐IgG appeared in the micro‐pores of SD mice skin within 4 hours after treatment in vivo. After 24 hours, it was observed in the skin. In MRL/lpr mice, positive lupus band testing (LBT) could be found on the skin lesion after laser and T‐IgG external application. Conclusions Fractional Er:YAG laser can help antibodies (150 kDa) to implement effective and controllable transdermal delivery. LBT can be achieved in MRL/lpr mice using TDDS in vivo, which may contribute to the minimally invasive diagnosis of LE. Lasers Surg. Med. 51:268–277, 2019. © 2018 Wiley Periodicals, Inc.

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

“…However, recently it was shown that nivolumab and two other antibodies could be delivered by fractional lasers into pig or mouse skin in vitro and in vivo. 6,15,16 In a previous study, we showed enhanced uptake and biodistribution of nivolumab in vitro using AFL and intradermal pneumatic injection on pig skin. 6 However, the impact of AFL or intradermal injection on pharmacokinetics and biodistribution of nivolumab in vivo remains to be determined.…”

“…The molecular weight of antibodies like nivolumab are 150 kDa, being around 100–10,000 times larger than the above‐mentioned drugs. However, recently it was shown that nivolumab and two other antibodies could be delivered by fractional lasers into pig or mouse skin in vitro and in vivo 6,15,16 …”

Topical Delivery of Nivolumab, a Therapeutic Antibody, by Fractional Laser and Pneumatic Injection

“…In previous studies, LADD has shown successful delivery of several smaller molecules (130-1415 Da) [12][13][14][15][16], and a few studies have also described the topical delivery of antibodies [19,37,38]. Two of these were by use of Er:YAG lasers, one in porcine skin in vitro [19], and another into mouse skin [37]. Furthermore, two studies have investigated the combination of AFL and anti-PD-1 antibody treatment of tumors in mice [38,39].…”

Optical Imaging Visualizes a Homogeneous and Horizontal Band-Like Biodistribution of Large- and Small-Size Hydrophilic Compounds Delivered by Ablative Fractional Laser

“…The interest in laser-assisted delivery of very large molecules such as antibodies (150 kDa) has increased in the past 5 years [ 6 , 10 , 11 , 12 ]. Topical delivery of therapeutic antibodies could be an advantage for the treatment of various skin diseases, providing a topical, targeted treatment compared to systemic administration, whereby possible side effects might be avoided.…”

“…Topical delivery of therapeutic antibodies could be an advantage for the treatment of various skin diseases, providing a topical, targeted treatment compared to systemic administration, whereby possible side effects might be avoided. Three LADD studies successfully demonstrated the delivery of antibodies using an Er:YAG laser [ 6 , 11 , 12 ] and two studies from our lab showed delivery of the anti-PD-1 antibody nivolumab with an ablative fractional CO 2 laser [ 13 , 14 ]. Further, a recent study showed reduced tumor growth in mice after treatment with an ablative fractional CO 2 laser, followed by topical application of anti-PD-1 antibody coated patches, indirectly indicating a successful delivery of the anti-PD-1 antibody into mouse tumors [ 10 ].…”