Rheumatoid arthritis (RA), is a chronic inflammatory autoimmune disease, that affects, approximately, 0.46–1% of the population [1]. Although the primary manifestation of the disease occurs in the joint, the RA has an extra-articular process, which include damages to the heart [2], lung [3], kidney [4], eye [5], skin [6] and nervous system [7]. In most of the cases, RA is characterized by damage in the locomotor system, loss of function (joint instability or joint ankylosis) and severe pain [9], [8], which impact the patient’s life.

RA therapy involves non-steroidal anti-inflammatory drugs (NSAIDs) for pain control, and disease-modifying anti-rheumatic drugs (DMARDs) such as glucocorticoids and methotrexate, leflunomide, sulfasalazine among others.[12], [10], [11]. However, the chronic use of glucocorticoids frequently present serious side effects and poor tolerability. When the conservative therapeutic scheme fails, the use of biological DMARDs is indicated, especially immunosuppressants and TNF-α and IL-6 blockers [9], [12], [11], [13]. In addition, current therapies for RA are limited by low drug bioavailability, high drug clearance, and dose-limiting adverse effects [14].

Regarding the economic aspect RA is responsible for very high costs arising from treatment as well as the loss of patient productivity [16], [15]. In 1991, Allaire et al. [15] estimated the lifetime medical care charges at $US 12,578 per patient. In 2018 the treatment cost was almost the same $US 12,509 [17]. However, with the insertion of biologic disease-modifying antirheumatic drugs (bDMARDs) the cost jump to $US 36,053 [16]. Birmbaum et al. estimated the total annual societal costs of RA (direct, indirect, and intangible) up to $39.2 billion [17].

Despite advances in treatment, differences in patient responses, high treatment costs and gastrointestinal disorders promote a quest for the discovery and development of new drugs. This scenario stimulates the search for alternative therapies, therefore, plant-derived products that can modulate the expression of inflammatory signals have a potential against joint inflammation [[18].

Methyl gallate is a gallotannin, which belongs to the group of polyphenols [19], [20]. As a polyphenol, methyl gallate, has a potent antioxidant [21], anti-inflammatory [22], and immunomodulatory properties [23]. In terms of pharmaceutical products, the formulation of antioxidant compounds is quite challenge [24]. In addition, the solubility and pharmacokinetics can be widely changed in terms of pharmaceutical formulations. To overcome these issues, the formulation of methyl gallate into nanomicelles may represent an important aspect. Nanomicelles are self-assembling nanosized colloidal dispersions with a hydrophobic core and hydrophilic shell [25]. In general, they are biocompatible [27], [26], [28], non-toxic [29] and biodegradable [31], [30] nanostructures.

In this study, we have produced, fully characterized, and evaluated in vitro and in vivo, the effect of methyl gallate nanomicelles (Nano-Methyl Gallate - NMG) in zymosan-induced experimental arthritis in mice.