Design of chondroitin sulphate coated proglycosomes for localized delivery of tofacitinib for the treatment of rheumatoid arthritis

[Display omitted] Long-term oral tofacitinib (TOF) administration has been linked to serious side effects majorly immunological suppression. The aim of this work was to enhance the therapeutic efficacy of TOF by chondroitin sulphate (CS) coated proglycosomes through the anchoring of high-affinity CS to CD44 receptors on immune cells in the inflammatory region. The CS was coated onto the TOF-loaded proglycosomes (CS-TOF-PG) formulations and they were evaluated for in vitro drug release, ex vivo (permeation, dermatokinetics) studies. In vivo efficacy studies were carried out in Freund's complete adjuvant (CFA) induced arthritis model. The optimized CS-TOF-PG showed particle sizes of 181.13 ± 7.21 nm with an entrapment efficiency of 78.85 ± 3.65 %. Ex-vivo studies of CS-TOF-PG gel exhibited 1.5-fold high flux and 1.4-fold dermal retention compared to FD-gel. The efficacy study revealed that CS-TOF-PG showed a significant (P