Microneedles enhance topical delivery of 15-deoxy-Δ 12,14 -prostaglandin J 2 and reduce nociception in temporomandibular joint of rats

Macedo, Cristina Gomes de; Jain, Amit; Franz-Montan, Michelle; Napimoga, Marcelo Henrique; Clemente-Napimoga, Juliana Trindade; Gill, Harvinder Singh

doi:10.1016/j.jconrel.2017.06.031

Cited by 17 publications

(11 citation statements)

References 36 publications

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“…In rats, reduction in nociception compared to intra temporomandibular join injection was observed, besides antiinflammatory effect, with reduced levels of tumor necrosis factor-α and interleukin-1 beta (Macedo et al, 2017) aminolevulinate (MAL) in ex vivo human skin (Osman-Ponchet et al, 2017). Abrasion of the skin using 10 passages of a commercial pad (Ambu® Unilect™ 2121M) followed by the application of a MAL cream (100 mg/cm²) for 2.5 h was also performed for comparison.…”

Section: Comparative Studies and Combination Methodsmentioning

confidence: 99%

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Physical methods for topical skin drug delivery: concepts and applications

Petrilli

Lopez

2018

Braz. J. Pharm. Sci.

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Topical drug delivery is an interesting approach to treat skin diseases and to avoid pain and low patient compliance in cases where a systemic delivery is required. However, the stratum corneum, which is the outermost skin layer, strongly protects the body from the entrance of substances, especially those hydrophilic. In this context, different physical methods have been studied to overcome the stratum corneum barrier and facilitate penetration of drugs into or through the skin. Among them, iontophoresis, low-frequency ultrasound and microneedles have been widely employed for transdermal drug delivery. More recently, they are also studied to aid in the treatment of dermatological disorders, such as skin tumors and inflammation. Basically, iontophoresis refers to the movement of charged and non-charged hydrophilic molecules through the skin due to the application of a low constant electric current and the contributions of electromigration and electroosmosis. In low-frequency ultrasound, cavitation is the main mechanism for skin permeabilization that consists on the formation of microbubbles that disorganize the stratum corneum. Microneedles are microprojections, minimally invasive, that can be designed with different lengths, materials and geometry to increase skin permeability. In this review, concepts, mechanisms and applications of these three physical methods will be presented and discussed with focus on their use in dermatological treatments. Moreover, comparative studies using different physical methods will be presented and also some clinical perspectives will be addressed.

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Section: Comparative Studies and Combination Methodsmentioning

confidence: 99%

“…Another usually reported application is the use for topical pain management (Macedo et al, 2017). Since some anesthetic drugs present rapid clearance from dermis or blood, strategies to overcome this hurdle and thus prolong anesthetic effect are promising.…”

Section: Microneedlesmentioning

confidence: 99%

Physical methods for topical skin drug delivery: concepts and applications

Petrilli

Lopez

2018

Braz. J. Pharm. Sci.

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“…We have previously observed a similar prolongation of antinociception (up to 6 hours) when we used MNs to topically deliver an anti-inflammatory compound, 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ) (Macedo et al, 2017). One explanation could be that when liquid is injected, the liquid can leave Fig.…”

Section: Discussionmentioning

confidence: 58%

“…Thus, there is need for both a pharmacological agent and a simple, painless, and possibly self-administrable method for administering the pharmacological agent. To facilitate delivery of drugs in a painless manner, we recently proposed microneedles (MNs) as a strategy for drug delivery to the periarticular tissues of the TMJ (Macedo et al, 2017). An MN patch consists of micron-scaled needles designed to rupture the stratum corneum layer of the skin.…”

Section: Introductionmentioning

confidence: 99%

“…MNs are painless (Gill et al, 2008) and are preferred by patients over hypodermic injections (Birchall et al, 2011). We have previously demonstrated that by creating microscopic holes in the skin covering the TMJ by application of MNs and then topically applying 15-deoxy-D 12,14 -prostaglandin J 2 , development of inflammatory pain can be prevented in the rat TMJ (Macedo et al, 2017). Lidocaine is a common analgesic, and it has been delivered into the skin using microneedles for pain management (Gupta et al, 2012;Ma and Gill, 2014;Kathuria et al, 2016;Zhan et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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

Abdalla

Jain

Napimoga

et al. 2019

J Pharmacol Exp Ther

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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.

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