In vivo dermal delivery of bleomycin with electronic pneumatic injection: drug visualization and quantification with mass spectrometry

Liora Bik*, Martijn van Doorn, Anders C.N. Hansen, Christian Janfelt, Uffe H. Olesen, Merete Haedersdal, Catharina M. Lerche, Kristoffer Hendel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
37 Downloads (Pure)

Abstract

Background: Intralesional bleomycin (BLM) administration by needle injection is effective for keloids and warts but has significant drawbacks, including treatment-related pain and operator-depended success rates. Electronic pneumatic injection (EPI) is a promising, less painful, needle-free method that potentially enables precise and controlled dermal drug delivery. Here, we aimed to explore the cutaneous pharmacokinetics, biodistribution patterns, and tolerability of BLM administered by EPI in vivo. Research Design and Methods: In a pig model, EPI with BLM or saline (SAL) were evaluated after 1, 48 and 216 hours. Mass spectrometry quantification and imaging were used to assess BLM concentrations and biodistribution patterns in skin biopsies. Tolerability was assessed by scoring local skin reactions (LSR) and measuring transepidermal water loss (TEWL). Results: Directly after BLM injection a peak concentration of 109.2 µg/cm3 (43.9–175.2) was measured in skin biopsies. After 9 days BLM was undetectable. EPI resulted in a focal BLM biodistribution in the mid-dermal delivery zone resembling a triangular shape. Mild LSRs were resolved spontaneously and TEWL was unaffected. Conclusions: BLM administered by EPI resulted in quantifiable and focal mid-dermal distribution of BLM. The high skin bioavailability holds a great potential for clinical effects and warrants further evaluation in future human studies.

Original languageEnglish
Pages (from-to)213-219
Number of pages7
JournalExpert Opinion on Drug Delivery
Volume19
Issue number2
DOIs
Publication statusPublished - 8 Feb 2022

Bibliographical note

Funding Information:
This work was supported by the Candys Foundation under Grant [17-236]. The authors like to thank Diana Høeg for her technical assistance during this study. In addition, support from the Carlsberg Foundation, Independent Research Fund Denmark | Technology and Production Sciences (grant no. 9041-00203B)) and the Lundbeck Foundation (R307-2018-3318) is gratefully acknowledged.

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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