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

Area of Science:

• Dermatology
• Pharmaceutical Sciences
• Nanotechnology

Background:

• Basal cell carcinoma (BCC) is the most common human skin cancer.
• Topical imiquimod offers a non-invasive treatment option, but is FDA-approved only for superficial BCC.
• Limited skin permeation of topical imiquimod hinders its efficacy for deeper BCC treatment.

Purpose of the Study:

• To assess imiquimod permeation from Aldara™ cream in skin depth and lateral distribution.
• To investigate a microneedle device as a strategy to enhance intradermal imiquimod delivery.
• To evaluate the role of HPLC and ToF-SIMS in mapping drug permeation.

Main Methods:

• In vitro Franz cell studies with HPLC analysis to quantify imiquimod recovery.
• Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for chemical imaging of skin samples.
• Tape stripping and microneedle pre-treatment of skin for permeation studies.

Main Results:

• Over 80% of topical imiquimod remained on the skin surface, with limited and non-uniform permeation into deeper skin layers.
• Microneedle pre-treatment resulted in approximately three times higher imiquimod recovery in tape strips and skin.
• ToF-SIMS imaging confirmed imiquimod presence in microneedle channels and lateral diffusion into the epidermis.

Conclusions:

• Topical imiquimod cream exhibits poor skin penetration, necessitating enhanced delivery strategies.
• Microneedle pre-treatment effectively enhances intradermal delivery of imiquimod.
• ToF-SIMS is a valuable tool for visualizing and quantifying drug permeation in skin.