Development of dissolving and hydrogel-forming microneedles for transdermal delivery of non-ergoline dopamine agonists

Continuous dopaminergic stimulation (CDS) stands as the most effective treatment due to providing controlled DRT, yet is limited to a few highly invasive, complex, inconvenient and non-universal infusions via pneumatic pump. Transdermal drug delivery provides a natural solution to many of these limitations, by being non-invasive, simple, convenient, and capable of sustained drug delivery. Yet it remains completely unexploited in this area, due to the narrow range of physicochemical characteristics that permit permeation across the skin.

Microneedle array patches (MAPs) are micro-projections (< 1 mm) that bypass the principal barrier of the skin, the stratum corneum, and significantly broaden the scope of transdermal drug delivery. Within this thesis, two highly efficacious non-ergoline DAs with limited modes of administration, apomorphine hydrochloride (APO) and ropinirole hydrochloride (ROP), were employed as model compounds in the exploration of novel MAP-based CDS strategies.

Specifically, APO and ROP were incorporated into dissolving-MAP (D-MAP) and hydrogel-forming-MAP (HF-MAP) systems that were evaluated through in vitro, ex vivo and in vivo experimentation. In Sprague-Dawley rats, MAPs matched or outperformed systemic drug exposure of conventional subcutaneous (SC) APO and peroral (PO) ROP, and a single MAP administration reduced peak plasma concentration and maintained therapeutic plasma levels for up to five days.

These MAPs may deliver therapeutic doses to humans in clinically feasible patch sizes. Therefore, this thesis provides compelling evidence that MAPs may be an effective novel modality for CDS.<br><br><i>Thesis is embargoed until 31 July 2031.</i><br>