Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis
| Autor: | Elias Fattal, Nicolas Tsapis, Marion Espéli, Pierre Chaminade, Françoise Gaudin, Mujeeb ur-Rehman, Sonia Abreu, Simona Mura, Mathilde Lorscheider, Ivana Stolfa |
|---|---|
| Přispěvatelé: | Institut Galien Paris-Sud (IGPS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), H.E.J. Research Institute of Chemistry [Karachi, Pakistan], International Center for Chemical and Biological Sciences [Karachi, Pakistan], Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Etudes des Techniques et Instruments d'Analyse Moleculaire (LETIAM), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Chimie Analytique Pharmaceutique - Faculté de Pharmacie (Lip(Sys)2), Université Paris-Sud - Paris 11 (UP11), Groupe de Chimie Analytique de Paris-Sud, TSAPIS, Nicolas, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Anti-Inflammatory Agents Palmitates Pharmaceutical Science Arthritis Inflammation 02 engineering and technology Pharmacology [SDV.SP.PG] Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology Dexamethasone Arthritis Rheumatoid 03 medical and health sciences Mice Pharmacokinetics medicine Animals 030304 developmental biology Autoimmune disease 0303 health sciences Drug Carriers Chemistry Cartilage 021001 nanoscience & nanotechnology medicine.disease Arthritis Experimental 3. Good health medicine.anatomical_structure RAW 264.7 Cells [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology Mice Inbred DBA Rheumatoid arthritis Nanoparticles Joints medicine.symptom 0210 nano-technology Glucocorticoid medicine.drug |
| Zdroj: | Journal of Controlled Release Journal of Controlled Release, Elsevier, 2019, 296, pp.179-189. ⟨10.1016/j.jconrel.2019.01.015⟩ Journal of Controlled Release, 2019, 296, pp.179-189. ⟨10.1016/j.jconrel.2019.01.015⟩ |
| ISSN: | 0168-3659 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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