Micro-Molded Polyacrylamide Microneedle Patches – an Effective Platform for Delivery of the Anti-Depressive Drug Agomelatine: An in Vitro/In Vivo Evaluation Publisher

Summary: Could dissolving microneedles deliver antidepressants? A polymer patch released drug and improved a behavioral measure in animals; human safety and benefit remain unknown. #DrugDelivery #MentalHealth

Taghvaei T ; Varshosaz J ; Mesripour A ; Renani A M
Source: RSC Pharmaceutics Published:2026

Abstract

Major depressive disorder (MDD) continues to be among the largest contributors to disability worldwide and frequently necessitates long-term pharmacotherapy. Most antidepressants with clinical effectiveness, however, suffer from low oral bioavailability, which is primarily attributed to their extensive first-pass metabolism. The present investigation was designed to evaluate the suitability of polyacrylamide (PAAM) for production of microneedle (MN) patches by the micro-molding technique for transdermal delivery of antidepressant drugs to increase their therapeutic efficacy. Dissolvable MNs were fabricated using the micro-molding technique with varying ratios of PAAM and polyvinyl alcohol (PVA). Mechanical properties, drug loading, in vitro permeation, skin penetration, and swelling behaviour were assessed. Finally, behavioural effects of the MN patches were evaluated in a dexamethasone-induced mouse model of depression using locomotor activity and forced swim tests. The optimized MN formulation consisting of 1% PVA and 4% PAAM exhibited approximately 62% drug loading efficiency, 47.5% permeation over 12 hours, mechanical resistance up to nearly 30 N and skin penetration capability. The permeation kinetics followed a first-order model, indicating a concentration-dependent permeation behaviour. Stability tests confirmed structural integrity and drug retention under accelerated conditions. Analysis of behavioural tests in an animal model of depression demonstrated that MN patches substantially reduced immobility time in the forced swim test without altering general locomotor activity, indicating antidepressant efficacy without central stimulation. Micro-molded dissolvable MN patches of PAAM present a promising alternative to the oral administration pathway of anti-depressant drugs. This journal is © The Royal Society of Chemistry, 2026.