Human Serum Albumin-coated macromolecular niosomes for enhanced immunotherapeutic efficacy in rheumatoid arthritis: optimization, characterization and in-vivo assessment

The purpose of this study was to design and optimize Baricitinib-loaded biomimetic (BCTB) niosomes for treatment of complete Freund's adjuvant (CFA)-induced rheumatoid arthritis (RA) in a rat model that mimics human joint inflammation. To enhance therapeutic efficacy and reduce infection risks, Human-Serum-Albumin (HSA)-decorated BCTB-loaded niosomes were formulated and evaluated against marketed BCTB tablets. Niosomes were developed using sonication followed by reverse-phase evaporation method and optimized via Central-Composite-Design. They were characterized for vesicle-size, zeta-potential, entrapment efficiency, morphology, in-vitro release, and molecular interactions (FTIR, DSC, XRD). In-vivo evaluation was conducted on Wistar rats, assessing interleukin-6 levels, body weight changes, arthritic index, radiographic findings, hematological parameters, and histopathology of rear paw joints. Optimized niosomes exhibited spherical morphology with a vesicle-size of 161.7 ± 0.1nm, PDI 0.145 ± 0.013, zeta-potential -52 ± 7.68mV, and high entrapment efficiency (93.40 ± 1.8%). FTIR, DSC, and XRD confirmed no significant drug-excipient interactions. HSA-decoration enhanced therapeutic effects of BCTB by prolonging drug release, mitigating adverse effects, and improving disease outcomes. BCTB niosomes significantly alleviated clinical and histopathological signs of RA, showing comparable efficacy to marketed BCTB tablets in 2mg/kg treated group. The following results prove that, BCTB-loaded niosomes as a targeted drug delivery platform for RA treatment, offering improved bioavailability, sustained release, and reduced systemic toxicity.