Dissolving microarray patch-mediated transdermal delivery of anti-Parkinson's agents

Abstract

The prevalence of Parkinson’s disease (PD) is regarded as one of the most significant challenges for global health, affecting approximately ten million people worldwide. Rotigotine (RTG) is a representative dopamine agonist, the first new chemical entity that is only formulated as a transdermal patch (Neupro®, 10 – 40 cm2) for PD treatment. However, the once-daily transdermal administration could be challenging for PD patients as it may likely become a life-long medication. Furthermore, studies have revealed that long-term repeated transdermal administration can induce application-site skin irritations, leaving the development of alternative formulations with prolonged release and reduced dosing frequency as a pressing issue. Therefore, RTG was formulated into a nanosuspension (NS) formulation and further loaded into dissolving microarray patches (MAPs) that can deposit the drug payload in the skin dermal layer and potentially release the drug in an extended behaviour. The simultaneous delivery of levodopa (LD) and its decarboxylase inhibitor, carbidopa (CD), remains the gold standard therapy for PD. However, the fluctuated pharmacokinetic profile of orally-administered LD can lead to motor complications such as ‘wearing-off’ periods. The currently marketed LD/CD intestinal gel (Duodopa®) offers an option to bypass the oral administration route and facilitate a continuous LD delivery, which gives a more stable plasma concentration than the oral formulation Sinemet®. However, Duodopa® therapy involves an invasive surgical procedure to implant a jejunal percutaneous endoscopic gastrostomy tube into the small intestine through which LD and CD are infused. Thus, a dissolving MAP formulation was developed for the simultaneous delivery of LD and CD. Formulated MAPs consist of 256 needles (16 x 16, 0.5 cm2) and were investigated in terms of various properties as well as ex vivo studies and in vivo pharmacokinetic profiles. This original approach offers a solution to deliver these anti-Parkinson’s agent transdermally as alternatives to the conventional formulations.

Thesis embargoed until 31st December 2029

Date of Award	Dec 2023
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Eneko Larrañeta (Supervisor) & Ryan Donnelly (Supervisor)