TY - JOUR

T1 - Electronic Pneumatic Injection-Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

AU - Bik, Liora

AU - van Doorn, Martijn B.A.

AU - Biskup, Edyta

AU - Ortner, Vinzent K.

AU - Haedersdal, Merete

AU - Olesen, Uffe H.

N1 - Publisher Copyright: © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC

PY - 2021

Y1 - 2021

N2 - Background and Objectives: Electronic pneumatic injection (EPI) is a technique for dermal drug delivery, which is increasingly being used in clinical practice. However, only few studies have been reported on cutaneous drug distribution and related clinical endpoints. We aimed to visualize the immediate cutaneous drug distribution, changes in skin architecture, and related clinical endpoint of EPI. Study Design/Materials and Methods: Acridine orange (AO) solution was administered to ex vivo porcine skin by EPI at pressure levels from 4 to 6 bar with a fixed injection volume of 50 µl and nozzle size of 200 µm. Immediate cutaneous distribution was visualized using ex vivo confocal microscopy (EVCM). Changes in skin architecture were visualized using both EVCM and hematoxylin and eosin-stained cryosections. Results: The defined immediate endpoint was a clinically visible papule formation on the skin. The pressure threshold to consistently induce a papule was 4 bar, achieving delivery of AO to the deep dermis (2319 µm axial and 5944 µm lateral distribution). Increasing the pressure level to 6 bar did not lead to significant differences in axial and lateral dispersion (P = 0.842, P = 0.905; respectively). A distinctively hemispherical distribution pattern was identified. Disruption of skin architecture occurred independently of pressure level, and consisted of subepidermal clefts, dermal vacuoles, and fragmented collagen. Conclusions: This is the first study to relate a reproducible clinical endpoint to EPI-assisted immediate drug delivery using EVCM. An EPI-induced skin papule indicates dermal drug delivery throughout all layers of the dermis, independent of pressure level settings. Lasers Surg. Med.

AB - Background and Objectives: Electronic pneumatic injection (EPI) is a technique for dermal drug delivery, which is increasingly being used in clinical practice. However, only few studies have been reported on cutaneous drug distribution and related clinical endpoints. We aimed to visualize the immediate cutaneous drug distribution, changes in skin architecture, and related clinical endpoint of EPI. Study Design/Materials and Methods: Acridine orange (AO) solution was administered to ex vivo porcine skin by EPI at pressure levels from 4 to 6 bar with a fixed injection volume of 50 µl and nozzle size of 200 µm. Immediate cutaneous distribution was visualized using ex vivo confocal microscopy (EVCM). Changes in skin architecture were visualized using both EVCM and hematoxylin and eosin-stained cryosections. Results: The defined immediate endpoint was a clinically visible papule formation on the skin. The pressure threshold to consistently induce a papule was 4 bar, achieving delivery of AO to the deep dermis (2319 µm axial and 5944 µm lateral distribution). Increasing the pressure level to 6 bar did not lead to significant differences in axial and lateral dispersion (P = 0.842, P = 0.905; respectively). A distinctively hemispherical distribution pattern was identified. Disruption of skin architecture occurred independently of pressure level, and consisted of subepidermal clefts, dermal vacuoles, and fragmented collagen. Conclusions: This is the first study to relate a reproducible clinical endpoint to EPI-assisted immediate drug delivery using EVCM. An EPI-induced skin papule indicates dermal drug delivery throughout all layers of the dermis, independent of pressure level settings. Lasers Surg. Med.

KW - biodistribution

KW - dermatology

KW - device

KW - drug delivery

KW - electronically-controlled

KW - ex vivo confocal microscopy

KW - needle-free injection

KW - pneumatic device

KW - skin

U2 - 10.1002/lsm.23279

DO - 10.1002/lsm.23279

M3 - Journal article

C2 - 32515075

AN - SCOPUS:85086092581

VL - 53

SP - 141

EP - 147

JO - Lasers in Surgery and Medicine

JF - Lasers in Surgery and Medicine

SN - 0196-8092

IS - 1

ER -