Dexamethasone palmitate

Dexamethasone palmitate is a highly lipophilic glucocorticoid prodrug. Dexamethasone palmitate exhibits 47-fold lower affinity for the glucocorticoid receptor compared to Dexamethasone. Dexamethasone palmitate can be hydrolyzed by esterases in inflamed tissues to the active metabolite dexamethasone, exerting anti-inflammatory and immunosuppressive effects. Dexamethasone palmitate can inhibit macrophage chemotaxis, phagocytosis, and reactive oxygen species release. Dexamethasone palmitate can be used in related research on rheumatoid arthritis, graft-versus-host disease, macular edema, and sudden sensorineural hearing loss^[1-4].

In vitro, treatment of macrophages activated with 100ng/mL LPS and 20ng/mL IFN-γ with 25μM Dexamethasone palmitate for 6-24 hours promoted rapid cell detachment from culture plates and reduced macrophage viability^[5]. Treatment of RAW264.7 cells activated with 0.1μg/mL LPS with 100μg/mL Dexamethasone palmitate nanoparticles for 24 hours reduced TNF-α and MCP-1 secretion levels^[6].

In vivo, intravitreal injection of 4μg Dexamethasone palmitate (0.5μL) immediately after laser-induced choroidal neovascularization in the right eye of Brown Norway rats. Dexamethasone palmitate reduced fluorescein leakage scores and decreased choroidal neovascularization volume^[7]. Intravenous injection of 10mg/kg Dexamethasone palmitate on day 7 and day 14 after transplantation in C57BL/6J mice with lethal graft-versus-host disease (GVHD). Dexamethasone palmitate reduced clinical GVHD scores, decreased skin and intestinal tissue damage and F4/80⁺ macrophage numbers, and increased survival rate^[8]. Inhalation of solid lipid nanoparticles containing Dexamethasone palmitate (5, 10, or 15mg/kg) via mesh nebulizer for 20 minutes in C57BL/6JNarl mice with intratracheal LPS-induced lung inflammation. Dexamethasone palmitate reduced TNF-α and IL-6 levels in bronchoalveolar lavage fluid, alleviated alveolar immune cell infiltration in lung tissue, and maintained alveolar and bronchiolar structural integrity^[9].

References:

[1] Ahn JH. Dexamethasone palmitate: A promising intratympanic treatment option for severe sudden hearing loss. Am J Otolaryngol. 2026 Jan-Feb;47(1):104766.

[2] Wang B, Huang C, Xu L, et,al. Bioequivalence evaluation of dexamethasone palmitate injections by intravenous injection in healthy Chinese volunteers: a 2-period crossover trial. Naunyn Schmiedebergs Arch Pharmacol. 2025 Dec;398(12):17735-17743.

[3] Lei Y, Cao YX, Xu CB, et al. The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice. Respir Res. 2008 Nov 3;9:71.

[4]Ono R, Sakamoto K, Doi T, et al. Dexamethasone palmitate for children with Epstein-Barr virus associated hemophagocytic lymphohistiocytosis. Int J Hematol. 2025 Feb;121(2):252-256.

[5] Nishiwaki S, Nakayama T, Murata M, et al. Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation: macrophage-targeted steroid therapy. Int J Hematol. 2012 Apr;95(4):428-433.

[6] Lorscheider M, Tsapis N, ur-Rehman M, et al. Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis. J Control Release. 2019 Apr 10;296:179-189.

[7] Daull P, Paterson CA, Kuppermann BD, et al. A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema. J Ocul Pharmacol Ther. 2013;29(2):258-269.

[8] Nishiwaki S, Nakayama T, Murata M, et al. Dexamethasone Palmitate Ameliorates Macrophages-Rich Graft-versus-Host Disease by Inhibiting Macrophage Functions. PLoS ONE. 2014 May 7;9(5):e96252.

[9] Chen H-H, Sang C-H, Chou C-W, et al. Solid Lipid Nanoparticles Loaded with Dexamethasone Palmitate for Pulmonary Inflammation Treatment by Nebulization Approach. Pharmaceutics. 2024 Jun;16(7):878.