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Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment

Al-Mayahy, Mohammed Hussain; Sabri, Akmal H.; Rutland, Catrin S.; Holmes, Amy; McKenna, John; Marlow, Maria; Scurr, David J.

Authors

Mohammed Hussain Al-Mayahy

Akmal H. Sabri

Amy Holmes

John McKenna

DAVID SCURR david.scurr@nottingham.ac.uk
Senior Research Fellow in Surface Analysis



Abstract

Basal cell carcinoma (BCC) is the most common skin cancer in humans. Topical treatment with imiquimod provides a non-invasive, self-administered treatment with relatively low treatment cost. Despite displaying excellent efficacy, imiquimod is only licensed by the FDA for superficial BCC. The current work employed HPLC and ToF-SIMS analysis to provide a novel assessment of imiquimod permeation from Aldara™ cream in skin depth and lateral distribution. Using Aldara™ cream and in vitro Franz cell studies with subsequent HPLC analysis, it is apparent that most of the topically applied imiquimod cream is left on the skin surface with more than 80% of the drug being recovered from skin wash. In addition, ToF-SIMS chemical imaging of recovered tape stripped skin samples illustrated significant detection of imiquimod signal over the entire skin area for the upper tape strips, whereas the deeper strips show large portions of the skin area without detected imiquimod. Given the limited permeation depth and non-uniform permeation observed at tape strips 6–18 when applied as a topical imiquimod cream, a permeation enhancement strategy utilising a skin pre-treatment with a microneedle device was investigated as a method to improve intradermal delivery. The recovered amount of imiquimod in tape strips and remaining skin determined by HPLC was approximately three times higher when Aldara™ was applied on microneedle pre-treated skin relative to intact skin. The ToF-SIMS ion images of the tape strips and cross-sections illustrated the existence of imiquimod in the microchannels which then laterally diffuses to peripheral epidermal strata. The current work demonstrates the first known attempt to enhance intradermal delivery of imiquimod using a microneedle device as well as underscoring the complementary role of ToF-SIMS analysis in chemically mapping imiquimod permeation into the skin with high sensitivity.

Journal Article Type Article
Publication Date 2019-06
Journal European Journal of Pharmaceutics and Biopharmaceutics
Print ISSN 0939-6411
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 139
Pages 33-43
APA6 Citation Al-Mayahy, M. H., Sabri, A. H., Rutland, C. S., Holmes, A., McKenna, J., Marlow, M., & Scurr, D. J. (2019). Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment. European Journal of Pharmaceutics and Biopharmaceutics, 139, 33-43. doi:10.1016/j.ejpb.2019.02.006
DOI https://doi.org/10.1016/j.ejpb.2019.02.006
Keywords Biotechnology; Pharmaceutical Science; General Medicine
Publisher URL https://www.sciencedirect.com/science/article/pii/S0939641118312475
Additional Information This article is maintained by: Elsevier; Article Title: Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment; Journal Title: European Journal of Pharmaceutics and Biopharmaceutics; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ejpb.2019.02.006; Content Type: article; Copyright: © 2019 Published by Elsevier B.V.

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