Development of dissolving microneedle patches containing nanosuspensions for the treatment of psoriasis

Abstract

Psoriasis is a chronic, recurring immune-mediated disorder that primarily affects the skin, nails, and joints. Currently, there is no cure for psoriasis, and therapy focuses on establishing and maintaining remission while minimising adverse events. Among the various treatment options available, topical treatment is considered the first-line therapy. In this thesis, two commonly used topical antipsoriatic drugs, salicylic acid (SA) and calcipotriol monohydrate (CPM) were investigated. Compared to traditional formulations, nanosuspensions could enhance efficacy and reduce side effects by reducing the dose, dosing frequency and dose dependence. However, nanosuspensions generally only enhance the dissolution rate and create temporary supersaturation and cannot penetrate the intact stratum corneum. Therefore, the use of a microarray patch (MAP) was employed in combination with the nanosuspension. SA and CPM nanosuspensions were developed using a rationalised laboratory-scale media milling system, and these nanosuspensions were then incorporated into dissolving MAPs. The MAPs used in this study were formulated using water-soluble polymers, specifically poly(vinyl pyrrolidone) and poly(vinyl alcohol). These MAPs were designed to deliver the two drugs through microneedle tips. The characterisation of the MAPs included assessments of drug content, mechanical and insertion properties, and importantly, ex vivo skin insertion and deposition studies. Additionally, the pharmacodynamics of CPM MAPs were evaluated using imiquimod-induced psoriasis-like Sprague Dawley rats as the animal model. This thesis provides convincing evidence that this novel delivery strategy could greatly enhance the delivery of drugs. CPM-loaded dissolving MAPs were as effective as the topical commercial ointment in restoring the performance of psoriasis skin to normal skin.

Thesis is embargoed until 31 July 2028.

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