Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception

Abstract

Coated microneedles have emerged as a promising drug delivery system for inflammatory pain treatment. We have previously shown that tramadol injection into the rat temporomandibular joint (TMJ) induces an antinociceptive and anti-inflammatory effect. In this study, microneedles coated with tramadol were investigated as a platform to treat TMJ pain. Male Wistar rats were administered tramadol using an intra-TMJ injection or with microneedles coated with tramadol, followed by 1.5% formalin nociceptive challenge administered 15 minutes later. The nociceptive behavior of rats was evaluated, and their periarticular tissues were removed after euthanasia for analysis. The duration of antinociceptive effect was determined by performing the formalin challenge at different time points extending up to 6 days post tramadol administration. Microneedles coated with tramadol produced an antinociceptive effect similar to injection of tramadol into the rat TMJ. Surprisingly, tramadol delivery using coated microneedles produced a more durable antinociceptive effect lasting as much as 2 days post tramadol delivery as compared with an antinociceptive effect lasting under 2 hours from intra-TMJ injection of tramadol. The proinflammatory cytokines tumor necrosis factor-a and interleukin-1b (IL-1b) were found to be reduced, whereas the anti-inflammatory cytokine IL-10 was found to be elevated in tramadol-treated groups. In conclusion, microneedles coated with tramadol can offer a therapeutic option for pain control of inflammatory disorders in the TMJ.

Microneedle Coating Methods: A Review with a Perspective

“…Likewise, Jain et al (2016) found that although the amount of 5aminolevulinic acid on a microneedle patch increased from 206-350 to 458-680 mg/patch, the delivery efficiency was found to have fallen from about 90% to 60% across the dose range. Abdalla et al (2019) also found a similar threshold effect. When they coated tramadol onto microneedles, they saw that at 20% or 30% (w/v) of tramadol in the coating solution, the resulting delivery efficiencies were similar and measured at 73% and 72%, translating into delivery of 139 and 185 mg tramadol, respectively.…”

“…Mass of material coated on microneedles. It has been observed that as the amount of material coated is increased, then after a certain threshold amount, the delivery efficiency decreases (Widera et al, 2006;Kim et al, 2014;Jain et al, 2016;Abdalla et al, 2019). In a study done by Widera et al (2006) it was seen that the delivery efficiency in hairless guinea pig skin using microneedles coated with radiolabeled ovalbumin was a function of the amount coated.…”

Microneedling in the relief of pain in arthritis: a brief review

“…In addition, intra-articular injection of tramadol significantly reduced the levels of the proinflammatory cytokines TNF-α and IL-1b. However, after 2 hours, the levels of TNF-α, IL-1b, and IL-10 were not significantly different from those of the nontreated group, indicating that the anti-inflammatory effect produced by intra-articular tramadol injection was of short duration, but after treatment with coated MNs, the levels of TNF-α and IL-1b were reduced and the levels of IL-10 were increased for up to 6 days 76 and the pain were controlled for a long period of time. This study shows that coated MNs have great potential for use in the treatment of pain in arthritis.…”

Drug delivery systems for treatment of temporomandibular joint osteoarthritis

“…Therefore, 15d-PGJ 2 cream associated with MNs is a promising patient-friendly therapeutic method for pain management related to TMJOA. Similarly, another study coats MNs with tramadol, and finds that tramadol delivery via MNs produce more durable antinociceptive effects than intra-TMJ injection of tramadol ( Abdalla et al, 2019 ). However, there is no coating on MN patches for controlling the cargo leakage, which results in burst release of cargoes at the beginning ( Wang et al, 2020 ).…”