Microneedle delivery of Iloperidone and Paliperidone for management of Schizophrenia and Bipolar disorder

Abstract

This research investigates microneedle-based transdermal delivery systems for Iloperidone (ILO) and Paliperidone palmitate (PLDN) as innovative alternatives to conventional therapies for the management of schizophrenia and bipolar disorder, where long-term treatment and poor patient adherence remain major challenges. Comprehensive analytical and bioanalytical methods (UV, HPLC, and LC MS) were developed and validated to ensure accurate quantification and stability assessment of both drugs. To enhance solubility and bioavailability, ILO was formulated as a hydroxypropyl-and#946;-cyclodextrin based multicomponent inclusion complex, while PLDN was incorporated into a zein maltodextrin nanocomplex. These optimized drug systems were successfully integrated into dissolving microneedles (DMNs) for both drugs and solid microneedle assisted transdermal films for ILO. The fabricated microneedles exhibited adequate mechanical strength, effective skin penetration, rapid pore recovery, and sustained drug release. In vitro and ex vivo studies confirmed significantly enhanced skin permeation and drug deposition compared to conventional formulations. Pharmacokinetic and pharmacodynamic evaluations demonstrated markedly higher plasma and brain drug concentrations, prolonged therapeutic effects, improved antipsychotic and antidepressant activity, and significant anti-inflammatory effects, with no evidence of skin irritation. Overall, this work establishes microneedle technology as a promising, minimally invasive, and patient-friendly platform for improving the bioavailability, therapeutic efficacy, and compliance of antipsychotic therapy, providing a strong foundation for future clinical translation in the treatment of schizophrenia and bipolar disorder. newline