Schizophrenia Treatment Based on Sustained Release of Risperidone from Poly(lactic-co-glycolic) Acid Implantable Microarray Patch.

Abstract

Schizophrenia is one of the most severe mental disorders, affecting approximately 24 million people worldwide. Conventional treatments, such as drug-loaded implants and intramuscular injections, have several limitations, including pain during administration and the need for medical professionals to perform the procedure. In this study, a poly(lactic-co-glycolic) acid (PLGA)-based implantable microneedle patch (IMN) was developed for the transdermal delivery of risperidone (RIS) as a treatment for schizophrenia. RIS IMNs were prepared by sequentially casting gel-based formulations into microneedle (MN) molds. The patches were then characterized using microscopy, differential scanning calorimetry, and infrared spectroscopy, as well as through evaluations of MN insertion and RIS release. A selected formulation was further tested by evaluating its cytocompatibility and its ability to deliver RIS in a rat animal model. The RIS IMN demonstrated excellent mechanical properties, successfully inserting up to 378 nm into model skin, which is crucial for effective transdermal drug delivery. A biocompatibility study using human dermal fibroblasts showed no cytotoxicity, with cell viability and proliferation being close to 100%. The optimized formulation achieved a sustained in vitro release over 7 days, while ex vivo skin deposition and permeation studies showed over 65% RIS delivery efficiency. In vivo animal studies confirmed that RIS IMNs maintained therapeutic plasma concentrations throughout the nine-day experiment, with C_max values of RIS and 9-OH RIS reaching 387.96 ± 194.02 and 139.89 ± 47.68 ng/mL at 6 and 96 h, respectively. In contrast, intramuscular injection showed a C_max of 1756.70 ± 246.06 and 1377.38 ± 160.78 ng/mL at 2 and 6 h but lost therapeutic effect after just 24 h. These findings suggest that RIS IMNs offer significant clinical benefits for patients with schizophrenia, providing prolonged therapeutic effects with a simple, self-administering drug delivery system, reducing the need for frequent medical interventions.