Imiquimod-loaded dissolving microneedles for enhanced dermal penetration in basal cell carcinoma immunotherapy: a feasibility and delivery study

Background: Topical imiquimod is widely used for the treatment of superficial basal cell carcinoma (sBCC) however its clinical efficacy is limited by variable stratum corneum penetration, prolonged treatment courses, and frequent local skin reactions. Improving intradermal delivery while reducing epidermal exposure could enhance both efficacy and tolerability in dermato-oncology. The aim of this study is to develop and characterise a dissolving microneedle (MN) platform for imiquimod delivery designed to improve dermal penetration and enable targeted local immunotherapy for basal cell carcinoma.
Schematic comparison of topical versus dissolving microneedle-mediated intradermal delivery of imiquimod. Topical application shows barrier-limited epidermal diffusion, while microneedles bypass the stratum corneum, enabling direct intradermal release and targeted distribution of imiquimod toward basal cell carcinoma lesions.

Methods: Imiquimod-loaded dissolving microneedles were fabricated using a sugar-based polymer matrix via micro-moulding technology. Microneedle morphology, mechanical integrity, and dissolution kinetics were assessed using optical and scanning electron microscopy. Drug incorporation and in-vitro release profiles were evaluated by UV-spectrophotometry and analytically validated using HPLC calibration modelling. Penetration depth and transport behaviour were examined using multilayered skin-mimetic models and diffusion-based receptor-phase analysis, with a topical imiquimod formulation used as a comparator.

Results: Imiquimod was successfully incorporated into dissolving microneedles with consistent uniform geometry and sufficient mechanical strength to penetrate the outer skin barrier. The MN arrays achieved rapid insertion and complete dissolution within minutes, enabling controlled release of imiquimod into deeper tissue layers. In-vitro release studies demonstrated sustained drug liberation from the microneedle matrix compared with free drug application, supporting enhanced intradermal availability. HPLC quantification confirmed reproducible drug loading and measurable receptor-phase recovery following microneedle delivery. Comparative analysis demonstrated formulation-dependent delivery performance, with microneedle-mediated delivery showing quantifiable intradermal transport relative to conventional topical application.

Formulation composition + quantified IMQ delivery (HPLC-derived concentration, mg/mL)
Conclusions: This feasibility and delivery study demonstrates that dissolving microneedles can bypass the stratum corneum to enable analytically validated, quantifiable intradermal delivery of imiquimod, offering a promising platform to optimise topical immunotherapy for basal cell carcinoma. The platform provides a translational foundation for subsequent pharmacodynamic and tumour-specific evaluation. This approach may improve local drug bioavailability while reducing superficial irritation, supporting further translational evaluation in dermato-oncology.

User License: Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)