315eP Pre-clinical feasibility and translational challenges of cytokine-loaded dissolvable microneedles for cutaneous immunotherapy

Background

Cytokines such as IFN-γ, TNF-α and IL-10 are central to tumour immune regulation, but systemic delivery is limited by short half-life and toxicity. Cutaneous malignancies such as melanoma, squamous cell carcinoma and basal cell carcinoma represent attractive targets for local immunotherapy. Dissolvable microneedles (MNs) could provide minimally invasive intradermal immunotherapy in cutaneous malignancies by enhancing immune activation while reducing systemic exposure. The aim of this study was to evaluate the feasibility and stability of cytokine incorporation into dissolvable MNs as a potential immuno-oncology drug delivery strategy.

Methods

Sugar-based MNs were fabricated by vacuum-assisted casting incorporating IFN-γ, TNF-α and IL-10. Mechanical strength and skin insertion were verified using excised porcine skin tissue. Cytokine recovery was assessed by ELISA immediately post-fabrication and after storage at room temperature and 45 °C for 1 week, 1 month and 2 months. Standards confirmed assay validity. Release behaviour was monitored during dissolution in aqueous media.

Results

MNs exhibited sharp geometry, reliable stratum corneum penetration, and sustained dissolution with release extending over 5 days. However, cytokine recovery was consistently below the ELISA detection limit (<LOD) across all formulations, both immediately after fabrication and following storage under all conditions tested. Standards retained activity, confirming instability was introduced during MN processing.

Conclusions

Although dissolvable MNs provided adequate mechanical performance and enabled sustained release over 5 days, cytokine incorporation resulted in complete loss of detectable protein. This pre-clinical feasibility study identifies stability as the major barrier to advancing cytokine-based immuno-oncology. Overcoming this challenge will require formulation optimisation such as stabilising excipients, improved drying processes, and alternative matrices before progressing to in vivo models and clinical translation of MN-mediated cytokine delivery in cutaneous cancer immunotherapy.