RT Journal Article
T1 Modulation of IFN-γ induced macrophage inflammatory responses via indomethacin-loaded NLCs for OA management
A1 Martínez Borrajo, Rebeca
A1 Rouco Taboada, Helena
A1 Virzì, Nicola Filippo
A1 Díaz Rodríguez, Patricia
A1 Landín Pérez, Mariana
K1 Nanostructured lipid carriers
K1 Cell uptake
K1 Osteoarthritis
K1 Macrophages polarization
K1 Intra-articular administration
AB Macrophages are the main cells present in the synovial membrane. They play an important role in the development and progression of osteoarthritis (OA). After the establishment of the disease macrophages mostly adopt a pro-inflammatory secretory phenotype (OA phenotype) further inducing cartilage degradation. Indomethacin (IND) is a non-steroidal anti-inflammatory drug (NSAID) able to inhibit the synthesis of prostaglandins mediated by both cyclooxygenase isoforms depicting a potent anti-inflammatory capacity. However, the lack of specificity and short half-like of free drugs within the joint cavity limits its utility in controlling inflammation after intra-articular administration. This study aims at developing IND loaded glycosylated nanostructured lipid carriers (NLCs) to selectively target macrophages and promote their reprogramming to an anti-inflammatory phenotype. This approach focused on the local administration of the NLCs, offers a promising therapeutic strategy for treating OA by modulating the inflammatory environment within the joint. NLCs will be designed by combining experimental and in silico docking analyses, and thoroughly characterized to obtain drug delivery systems with high stability and suitable physicochemical properties. The proposed mannose-functionalized systems exhibited adequate particle sizes (≈ 70 nm) and positive surface charges (> 20 mV) to be efficiently retained in the joint cavity. Moreover, the developed NLCs demonstrated effective and specific uptake by OA-like macrophages leading to a significant decrease in the secretion of the pro-inflammatory cytokines IL-6, IL-8 and TNF-α similarly to the free drug. Therefore, these systems effectively reprogrammed OA-associated macrophages to adopt a more regenerative phenotype, offering a promising strategy for managing inflammation in OA.
PB Elsevier
SN 0378-5173
YR 2024
FD 2024-10-10
LK https://hdl.handle.net/10347/40297
UL https://hdl.handle.net/10347/40297
LA eng
NO Martínez-Borrajo R, Rouco H, Virzì NF, Diaz-Rodriguez P, Landin M. Modulation of IFN-γ induced macrophage inflammatory responses via indomethacin-loaded NLCs for OA management. Int J Pharm. 2024 Dec 5;666:124823. doi: 10.1016/j.ijpharm.2024.124823. Epub 2024 Oct 11
NO Consellería de Innovación Program for the Grupos de Referencia Competitiva ED431C 2024/09 of Xunta de Galicia
DS Minerva
RD 29 abr 2026