Work

Diphenyl carbonate crosslinked β-cyclodextrin nanosponge-based topically applied gel for co-delivery of baricitinib and tenoxicam in rheumatoid arthritis

Year: 2025

Type: article

Abstract: The present study is aimed at developing baricitinib (BAR) and tenoxicam (TNX) loaded nanosponge (NS) gel for potential topical treatment of rheumatoid arthritis (RA). DPC crosslinked β-CD NS were synthesized at various molar ratios (1:2-1:20), with the 1:8 ratio showing the highest drug loading efficiency (67.0 ± 6.9% for BAR; 82.1 ± 6.8% for TNX). XRD and DSC analysis confirmed amorphization of drugs, SEM revealed porous morphology, DLS revealed particle sizes of 545.5 ± 16.4 nm (BAR-NS) and 585.2 ± 57.7 nm (TNX-NS) with zeta potentials of -11.1 ± 4.4 and -14.6 ± 3.9 mV, respectively. The optimized NS were formulated into topical gels, demonstrating sustained release (BAR: 77-90%; TNX: 96% within 12 h). In vivo evaluation using a CFA-induced RA rat model revealed that combined BAR-NS and TNX-NS gel (0.05/0.25% w/w) inhibited paw edema by >90% at day 25, significantly downregulated pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), restored IL-10, and normalized liver enzymes (ALT, AST, ALP). Histopathological analysis confirmed preservation of cartilage and bone with minimal synovial infiltration. In conclusion, combination of BAR-NS and TNX-NS gel showed synergistic anti-arthritic and anti-inflammatory effects, thus offering a potential topical alternative to conventional therapies for the management of RA.

Source: European Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ejps.2025.107418