A promising alliance in multiple sclerosis treatment. Microarray patch for the administration of beta interferon: A preclinical minipig study

Abstract

The transdermal delivery of large molecules such as proteins and vaccines faces enormous challenges and at the same time holds great potential for the non-invasive treatment of local and systemic diseases. To demonstrate the pharmaceutical utility of microarray patches (MAP) recombinant human beta interferon-1a (IFN) containing MAPs were prepared and used in an animal study. Serum IFN levels were measured for 5 days in minipigs which are the animal model most comparable to human skin. The peak IFN serum level, the maximum drug concentration (Cmax) and the time to reach the maximum concentration (Tmax) were 4.6 ng/mL and 2 h for the low-dose MAP group, respectively. The area under the curve (AUC) of this MAP group was 118 ng∗h/mL, while the intramuscular injection (IM) was 146 ng∗h/mL and the intradermal injection was 140 ng/mL.

IFN-MAPs did not damage the investigated application sites of the skin of the administered minipigs in any way. The results of this study show that Microarray patch technology have great potential to provide an alternative to injectable therapy systems.

Introduction

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system, causing inflammation, demyelination, and a range of neurological symptoms [1]. Beta interferon (IFN), a cytokine with immunomodulatory properties, has been a cornerstone in the treatment of multiple sclerosis [2]. Recombinant interferon beta is an effective and safe drug for the immunoprophylactic treatment of MS patients that can reduce the frequency and severity of relapses and delay the progression of the disease [3]. As several university research groups and research-based pharmaceutical manufacturers delve into innovative approaches to improve the effectiveness of MS treatment, microneedle systems coupled with beta interferon emerge as a promising alliance [4]. Especially because conventional injection methods may lead to challenges such as patient discomfort, injection site reactions, and poor compliance.

Microneedle systems offer an innovative solution to these issues by providing a less invasive and more patient-friendly means of drug administration [[5], [6], [7], [8]]. These minimally invasive devices consist of tiny needle-like structures, typically ranging from few hundreds of micrometers to 1 mm in length, designed to penetrate the outer layers of the skin [9]. Unlike traditional needles, microneedles often do not reach nerve endings, resulting in a painless or significantly less painful experience for the patient. The advantages of microneedle systems include enhanced patient compliance and the potential for self-administration. Another important advantage of microneedle systems is the enhancement of drug bioavailability [10] by bypassing the gastrointestinal tract and delivering medication directly to the systemic circulation or via triggering specific immunomodulating cells. However, microneedles ensure a more rapid onset of action and increased overall efficacy. This is particularly crucial in the management of multiple sclerosis, where timely intervention is essential to control disease progression and prevent relapses. In this article we report the administration of human beta interferon-1a via microarray patch technology in a preclinical study by the use of minipigs as one ideal animal model for transdermal drug administration [11].

Minipigs offer significant advantages for this type of study as their skin closely resembles human skin in terms of structure and thickness. They are also approved by regulatory authorities, allow for large-scale application, and rarely exhibit spontaneous skin changes [12]. As described by Wie et al. [13], smaller animals (e.g., mice and rats) demonstrate more pronounced viscoelastic behavior compared to larger animals such as minipigs. Consequently, minipig skin is recommended as a suitable model for preclinical testing of micro-devices. Preclinical or clinical studies involving microarray patches (MAPs) focusing on interferon remain scarce in the scientific literature. Kusamori et al. [14] reported the development of an interferon-alpha-coated non-dissolving MAP, which demonstrated comparable efficacy to subcutaneous injections in a rat model. With this study, we aim to contribute to the field by presenting the first administration of human beta interferon-1a via dissolvable polymer-based microarray patch technology in minipigs, yielding comparable blood levels to intramuscular and subcutaneous injections.

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Materials

Recombinant human interferon beta-1a (4.92 mg/ml, 229 MIU/mg, IFN) was provided by Biogen MA Inc (Cambridge, USA). Tween 80 and Glycerol were purchased from Merck (Darmstadt, Germany). Trehalose from Nagase Viita (Düsseldorf, Germany) and Kollidon 30 from BASF (Ludwigshafen, Germany). All other chemicals used were of analytical reagent grade.

Danny Brodkorb, Sebastian Scherr, Anna Schlüter, A promising alliance in multiple sclerosis treatment. Microarray patch for the administration of beta interferon: A preclinical minipig study, Journal of Drug Delivery Science and Technology, Volume 114, Part A, 2025, 107460, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107460.

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