Development of Dissolving Microneedles for local Methotrexate and lubricants Delivery: A Strategy for Improved Pain and Treatment Management of Rheumatoid Arthritis

Koochakkosari, Seyedsepehr; Poorkhalil, Ali; Tabesh, Hadi; Farrokhzad, Hasan; Bashiri Barazande, Mostafa; Golkar, Ali

Development of Dissolving Microneedles for local Methotrexate and lubricants Delivery: A Strategy for Improved Pain and Treatment Management of Rheumatoid Arthritis

Articles in Press

Document Type : Research Article

Authors

Seyedsepehr Koochakkosari ¹

Ali Poorkhalil ²

Hadi Tabesh ³

Hasan Farrokhzad ⁴

Mostafa Bashiri Barazande ¹

Ali Golkar ¹

¹ College of Interdisciplinary Science and Technology, University of Tehran, Tehran, Iran

² University of Tehran

³ biomedical engineering, College of Interdisciplinary Science and Technology, University of Tehran, Tehran, Iran

⁴ School of Chemical, Petroleum and Gas Engineering, Iran University of Science and Technology

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease affecting the synovial membrane and disrupting the healthy production of synovial fluid, the natural lubricant of joints. Conventional treatments based on methotrexate (MTX), despite their widespread use, are associated with limitations such as low bioavailability, high systemic toxicity, and poor tissue penetration. Furthermore, these methods primarily focus on inflammation reduction, often necessitating the concurrent administration of analgesics for pain relief. In this study, a dissolving microneedle patch was designed to co-deliver MTX and two lubricants, hyaluronic acid (HA) and glycerol. Mechanical testing revealed that the fabricated patch could withstand a force of 0.11 N per microneedle and effectively penetrate the initial four layers of Parafilm®, indicating its potential to penetrate joint tissue without fracture. In vitro release studies using rat skin demonstrated localized drug delivery, with 48.46% of MTX remaining in the tissue after release. Glycerol, in addition to contributing to lubrication, could potentially enhance patch's flexibility, enabling conformal adaptation to joints with varying curvatures. The developed MN patch, with its potential for simultaneous treatment and pain alleviation, offers a promising avenue for improving rheumatoid arthritis therapies and presents a suitable alternative to existing market treatments.

Keywords

Keywords Rheumatoid arthritis

Dissolving microneedles

Local drug delivery

Joint lubrication

Hyaluronic acid

Subjects