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oai:figshare.com:article/32805914 2026-10-01T16:11:54Z portal_1172 item_type_8 month_year_10_2026

Development of dissolving and hydrogel-forming microneedles for transdermal delivery of non-ergoline dopamine agonists Andrew P. Graham (2516167) PUREID: 690690243 Parkinson's Disease microneedle dissolving hydrogel apomorphine ropinirole continuous dopaminergic stimulation dopamine replacement therapy Parkinson's disease (PD) causes substantial morbidity and reduced quality of life (QOL). It is the second most common neurodegenerative disorder worldwide, with a rapidly increasing prevalence resembling a pandemic without an infectious cause. Current projections suggest that PD will be an increasingly significant global healthcare challenge for the future. Dopamine replacement therapy (DRT) effectively ameliorates impaired motor control, however, within 5 – 10 years up to 80% of patients develop acute motor fluctuations. These come in the form of hyperkinetic dyskinesias or hypokinetic ‘OFF’ periods, and are the main source of reduced quality-of-life (QOL). Despite numerous adjunctive treatment strategies, motor fluctuations remain considered an unmet clinical need. 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> 2026-10-01T16:11:54Z Text Thesis 10.17034/32805914.v1 https://figshare.com/articles/thesis/Development_of_dissolving_and_hydrogel-forming_microneedles_for_transdermal_delivery_of_non-ergoline_dopamine_agonists/32805914 All Rights Reserved Open Access after 2031-07-31