Fabrication of bergapten loaded microneedle patch and assessment of its anti-arthritic potential against complete Freund's adjuvant induced arthritis in Wistar rat.

Abstract

This research study was designed to fabricate bergapten-loaded biodegradable microneedle patches (BP-MNPs) and assess its anti-arthritic potential. The BP-MNPs were synthesized by solvent casting technique using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymers, followed by their characterization. The in vitro release study and stability study were also conducted. X-ray diffraction analysis of BP-MNPs showed a broad range of crystallographic planes, while SEM analysis showed unfractured, sharp tips with a length of 500 µm and a base of 200 µm. The anti-arthritic potential of BP-MNPs was investigated by inserting 0.15 ml of Complete Freund's adjuvant (CFA) into the tail vein of Wistar rats on day 1 to develop a CFA-induced arthritic model. Treatment begins on the 8th day and continues till the 28th day. Methotrexate was administered orally (1 mg/kg) as the standard treatment. The BP-MNPs significantly (p < 0.001-0.0001) decreased paw swelling, arthritic scoring, pain, and restored body weight compared to orally administered bergapten and the standard treatment. The blood parameters were also restored by BP-MNPs, along with the restoration of oxidative stress biomarkers in liver homogenate and neurotransmitter levels in sciatic nerve homogenate. Treatment with BP-MNPs notably (p < 0.0001) reduced the mRNA expression of IL-6, COX-2, TNF-α, and NF-κB, while upregulating IL-4 in contrast to disease control and standard treatment groups. Treatment with BP-MNPs also improved the histology of the ankle joint and sciatic nerve. It can be concluded from the current study data that BP-MNPs at a dose of 10 mg/kg exhibited significant anti-arthritic and anti-nociceptive responses in arthritic rats in contrast to bergapten and the standard drug.