Microneedle array patches for skin hyperthermia and enhanced intradermal drug delivery

Abstract

Microneedles (MN) arrays are micron-size needle arrays with length generally ranging between 50 μm and 2 mm. When applied to the skin surface, they pierce the stratum corneum creating micropores that can enhance the delivery of drugs into the viable skin layers. MN arrays offer great advantages for localised treatment of skin disorders which, in combination with skin hyperthermia can help inhibiting bacterial growth and induce apoptosis in cancer cells. In this thesis, new approaches to induce superficial and deep skin hyperthermia using gold nanorods (GnRs) were investigated. In addition, single needles, hollow and dissolving MN arrays for skin drug delivery were developed, aiming to enhance deposition of drugs in the dermis. GnRs were synthesized and loaded in hydrogels made from aqueous blends containing poly(methyl vinyl ether-co-maleic acid) and poly(ethylene glycol). These polymeric blends were used to fabricate films to heat up a thin skin model upon Near Infrared (NIR) laser irradiation. This technology circumvents skin deposition and injection of GnRs and, thereby, the uncertainty regarding their metabolism, safety and toxicity once they reach the systemic circulation. This approach was further improved in its use for skin hyperthermia, using GnRs coated on MN arrays where their efficacy heating up a thick skin model was confirmed. For intradermal drug delivery, hydrogel- forming single needles were fabricated, which were then coated with a model drug to investigate how deep these devices deliver the drug in a skin model. As the drug was coated and dried on the surface of needles, issues associated with hypodermic needles, such as stability of liquid formulations and generation of hazardous waste are avoided. When compared to a control formulation, single needles increased penetration depth of the drug significantly in the skin model, confirming the potential of coated polymeric needles for deep intradermal delivery. Finally, hollow polymeric MN arrays and dissolving MN arrays were fabricated to enhance the intradermal delivery of tofacitinib citrate, a drug for which clinical trials provide strong evidence for its effectiveness against inflammatory skin conditions. However, oral administration is not ideal due to reported side effects. Skin deposition studies showed that hollow MN arrays led to slightly higher deposition of drug in the dermis in comparison to a control cream. However, dissolving MN arrays showed superiority on this regard, providing proof of principle for intradermal delivery of tofacitinib citrate using MN arrays. Overall, the results shown in this thesis confirm the benefits of using MN arrays for skin hyperthermia and intradermal delivery and their potential future applications in the management of skin diseases.

Date of Award	Jul 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	EC/Horizon 2020 Marie Skłodowska-Curie actions
Supervisor	Ryan Donnelly (Supervisor) & Eneko Larrañeta (Supervisor)