Intradermal delivery of imiquimod using polymeric microneedles for basal cell carcinoma

Sabri, Akmal H.; Cater, Zachary; Gurnani, Pratik; Ogilvie, Jane; Segal, Joel; Scurr, David J.; Marlow, Maria

Abstract

Despite being one of the most efficacious drugs used in the treatment of basal cell carcinoma (BCC), imiquimod has limited cutaneous permeation. The current work presents the development of polyvinylpyrrolidone-co-vinyl acetate (PVPVA) microneedles loaded with imiquimod for improving intradermal delivery of imiquimod for the treatment of nodular BCC. In vitro permeation studies, using full thickness ex vivo porcine skin were used to evaluate the effectiveness of these imiquimod loaded polymeric microneedles in comparison to the topical application of commercial Aldara™ cream. HPLC analysis demonstrated similar intradermal permeation of imiquimod from Aldara™ cream and imiquimod-loaded microneedles despite the microneedle having a six-fold lower drug loading than the clinical dose of Aldara™ used for BCC management. In addition, ToF-SIMS analysis of skin cross sections demonstrated intradermal localisation of imiquimod following microneedle-based delivery while the Aldara™ treated skin showed the drug localised predominantly within the stratum corneum. ToF-SIMS analysis also demonstrated intradermal co-localisation of the PVPVA polymer, used in fabricating the microneedle, with imiquimod within the microneedle channels in a label-free manner. This study demonstrates that a polymeric microneedle system may be a viable approach to improving the intradermal delivery of imiquimod for the treatment of nodular BCC with lower drug loading.

Citation

Sabri, A. H., Cater, Z., Gurnani, P., Ogilvie, J., Segal, J., Scurr, D. J., & Marlow, M. (2020). Intradermal delivery of imiquimod using polymeric microneedles for basal cell carcinoma. International Journal of Pharmaceutics, 589, Article 119808. https://doi.org/10.1016/j.ijpharm.2020.119808

• Journal Article Type: Article
• Acceptance Date: Aug 20, 2020
• Online Publication Date: Sep 4, 2020
• Publication Date: Nov 15, 2020
• Deposit Date: Sep 25, 2020
• Publicly Available Date: Sep 5, 2021
• Journal: International Journal of Pharmaceutics
• Print ISSN: 0378-5173
• Electronic ISSN: 1873-3476
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 589
• Article Number: 119808
• DOI: https://doi.org/10.1016/j.ijpharm.2020.119808
• Keywords: Microneedles; Imiquimod; Basal cell carcinoma; Time-of-flight secondary ion mass spectrometry; Polyvinylpyrrolidone-co-vinyl acetate
• Public URL: https://nottingham-repository.worktribe.com/output/4913265
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0378517320307936
• Additional Information: This article is maintained by: Elsevier; Article Title: Intradermal delivery of imiquimod using polymeric microneedles for basal cell carcinoma; Journal Title: International Journal of Pharmaceutics; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ijpharm.2020.119808; Content Type: article; Copyright: © 2020 Elsevier B.V. All rights reserved.