RT Journal Article
T1 Sulfasalazine Microparticles Targeting Macrophages for the Treatment of Inflammatory Diseases Affecting the Synovial Cavity
A1 Villa Hermosilla, M. C.
A1 Fernández Carballido, Ana María
A1 Fernández-Carballido, Ana
A1 Hurtado, Carolina
A1 Barcia Hernández, Emilia
A1 Montejo, Consuelo
A1 Alonso, Mario
A1 Negro Alvarez, María Sofía Elisa
AB Rheumatoid arthritis (RA) is a chronic inflammatory disease with sulfasalazine (SSZ) extensively used for long-term treatment of both juvenile and adult RA. Its use is associated with adverse effects and toxicity due to its non-selective biodistribution. Macrophages play an important role in inflammatory processes. In order to target SSZ to macrophages in this work two microparticulate systems (MPs) are developed: SSZ-loaded PLGA MPs without and with α-tocopherol, with particle sizes lower than 5 μm and encapsulation efficiencies of 81.07 ± 11% and 63.50 ± 6.62%, respectively. Release of SSZ from MPs prepared with α-tocopherol was prolonged for 20 days. In RAW 264.7 cell macrophages MPs prepared with α-tocopherol were captured faster. Cell viability studies confirmed that SSZ-loaded MPs prepared without and with α-tocopherol did not produce cytotoxicity at the concentrations assayed. The anti-inflammatory activity of SSZ-loaded MPs was studied by quantifying interleukins IL-1, IL-6 and TNF-α in macrophages. All formulations produced a significant reduction of cytokine concentrations after 24 and 72 h, indicating that release of SSZ from the MPs was able to inhibit the inflammatory response induced by lipopolysaccharide (LPS). Gene expression of IL-1, IL-6 and TNF-α was decreased by SSZ-loaded MPs. SSZ-loaded MPs prepared with α-tocopherol will potentially allow increasing the residence time of SSZ in the synovial cavity, prolonging its duration of action, and reducing the adverse effects associated with its non-selective biodistribution.
PB MDPI
SN 1999-4923
YR 2021
FD 2021-06-24
LK https://hdl.handle.net/20.500.14352/7073
UL https://hdl.handle.net/20.500.14352/7073
LA eng
NO Complutense University of Madrid research group “Formulation and Bioavailability of New Drugs” (UCM 910939).
DS Docta Complutense
RD 3 may 2024