Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment link
طبية
European Journal of Pharmaceutics and Biopharmaceutics link
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Dr. David Scurr/ School of Pharmacy/ The University of Nottingham/ UK Dr. Maria Marlow/ School of Pharmacy/ The University of Nottingham/ UK
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 crosssections
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.