Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis

Mathilde Lorscheider (1, 2) , Nicolas Tsapis (2) , Mujeeb Ur-Rehman (1, 3) , Françoise Gaudin (4) , Ivana Stolfa (1, 2) , Sonia Abreu (5, 6) , Simona Mura (1, 2) , Pierre Chaminade (7, 6) , Marion Espéli (4) , Elias Fattal (2)

1 IGPS - Institut Galien Paris-Sud
2 IGPS - Institut Galien Paris-Saclay
3 H.E.J. Research Institute of Chemistry [Karachi, Pakistan]
4 Cytokines, chimiokines et immunopathologie
5 LETIAM - Laboratoire d'Etudes des Techniques et Instruments d'Analyse Moleculaire
6 Lip(Sys)2 - Lipides : systèmes analytiques et biologiques
7 Groupe de Chimie Analytique de Paris-Sud

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by joint inflammation, bone and cartilage erosion. The use of glucocorticoids in the treatment of RA is hampered by significant side effects induced by their unfavorable pharmacokinetics. Delivering glucocorticoids by means of nanotechnologies is promising but the encapsulation of highly crystalline and poorly water-soluble drugs results in poor loading and low stability. We report here the design of 130 nm nanoparticles made of solely dexamethasone palmitate, stabilized by polyethylene glycol-linked phospholipids displaying a negative zeta potential (−55 mV), high entrapment efficiency and stability over 21 days under storage at 4°C. X ray diffraction showed no crystallization of the drug. When incubated in serum, nanoparticles released free dexamethasone which explains the in vitro anti-inflammatory effect on LPS-activated RAW 264.7 macrophages. Moreover, we demonstrate in a murine collagen-induced arthritis model the improved therapeutic efficacy of these nanoparticles. Their passive accumulation in arthritic joints leads to disease remission and recovery of the joint structure at a dose of 1 mg/kg dexamethasone, without any adverse effects. Dexamethasone palmitate nanoparticles are promising in the treatment of inflammation in rheumatoid arthritis with a very significant difference occurring at the late stage of inflammation allowing to prevent the progression of the disease.

Domaines: Pharmacie galénique

Mathilde Lorscheider, Nicolas Tsapis, Mujeeb Ur-Rehman, Françoise Gaudin, Ivana Stolfa, et al.. Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis. Journal of Controlled Release, 2019, 296, pp.179-189. ⟨10.1016/j.jconrel.2019.01.015⟩. ⟨hal-02323608⟩