1. Academic Validation
  2. Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis

Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis

  • J Control Release. 2019 Feb 28;296:179-189. doi: 10.1016/j.jconrel.2019.01.015.
Mathilde Lorscheider 1 Nicolas Tsapis 1 Mujeeb Ur-Rehman 2 Françoise Gaudin 3 Ivana Stolfa 1 Sonia Abreu 4 Simona Mura 1 Pierre Chaminade 4 Marion Espeli 3 Elias Fattal 5
Affiliations

Affiliations

  • 1 Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Univ. Paris-Saclay, 92290 Châtenay-Malabry, France.
  • 2 Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Univ. Paris-Saclay, 92290 Châtenay-Malabry, France; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 3 INSERM UMR 996, Univ. Paris-Sud, Univ Paris-Saclay, 92140 Clamart, France.
  • 4 Lip (Sys)(2) EA7357, Lipides, Systèmes Analytiques et Biologiques, Univ. Paris-Sud, Univ. Paris-Saclay, 92290 Châtenay-Malabry, France.
  • 5 Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Univ. Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: elias.fattal@u-psud.fr.
Abstract

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.

Keywords

Arthritis; Glucocorticoid; Nanomedicines; Prodrug.

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