Development of novel nanoformulations for the effective treatment of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease leads to synovial joint inflammation and cartilage destruction. The main aim of this research work was to develop novel nano formulations for the effective treatment of RA upon topical and intravenous administrations. Topical nanoformulation focussed to overcome the solubility issue of methotrexate (MTX) and hypothesized to improve the permeation of MTX upon topical administration, through the development of cubosomes (lipidic nanoparticle having 3D bicontinuous cubic phase), whereas MTX and minocycline (MNC) loaded nanoparticle (MMNPs) for intravenous administration hypothesized to overcome the solubility issue of MTX and to control bacterial infection commonly associated with RA, thereby both formulations elicits better anti-arthritic potential. The particle size of MTX loaded cubosomes named as MTCs-1 to MTCs-8 ranged from 550 nm to 1130 nm and the zeta potential ranged from -33mV to -7.84 mV. The mean particle size of MMNPs named as MMNPs-1 to MMNPs-8 ranged from 125.0 nm to 185 nm and zeta potential ranged from -34 mV to -6 mV. A maximum percentage encapsulation of 92.94 ± 0.9% MTX was obtained for the MTCs-2 cubosomes. Whereas, in case of MMNPs the encapsulation efficiency was about 85 to 32 % for MTX and 60 to 30% for MNC. The morphology of MTCs-2 and MMNPs were analysed through hr-TEM. The in-vitro release profile of MTCs-2 showed an initial burst release of 80 % at 1.5 h, followed by a steady release upto 8 h in pH 7.4. The percentage cumulative drug release profile of MMNPs-2 showed a sustained release pattern newline