NANOEMULGEL-BASED DELIVERY OF 3-ACETYL-11-KETO-Β BOSWELLIC ACID: A STRATEGY FOR ENHANCED TRANSDERMAL DRUG DELIVERY AND ANTI-ARTHRITIC EFFICACY

Abstract

Background: Rheumatoid arthritis (RA) is an autoimmune condition that causes inflammation of the synovial membrane, leading to joint pain, swelling and destruction. 3-O-acetyl-11-keto-β-boswellic acid (AKBA), a constituent of Boswellia serrata, effective against inflammation and arthritis, but suffers from limited aqueous solubility and permeability through skin. In this regard, the objective of the current study was to prepare AKBA loaded nanoemulgel and explore its therapeutic potential in rheumatoid arthritis. Methods: An optimized AKBA nanoemulsion was added into gel matrix prepared with HPMC K15M and carbopol 940 to formulate nanoemulgels. These formulations were evaluated for physicochemical properties, in-vitro drug release and ex-vivo skin permeation. The optimized formulation was then tested in an arthritis animal model induced with complete freund’s adjuvant (CFA). Haematological, serological parameters were estimated and radiological, histopathological examination of ankle joints was also conducted. Results: Nanoemulgel formulation NG5 made of carbopol 940 was chosen as the optimized nanoemulgel in terms of physicochemical properties and drug release properties. NG5 had the following physical characteristics: pH of 6.11 ± 0.04, viscosity of 538.42 ± 2.84 cP and drug content of 105.12 ± 0.08%. The formulation had 93.42% drug diffusion cumulatively over 24 h. In ex-vivo permeation studies, cumulative permeation was found to be 1487.32 ± 8.46 µg/cm², with a steady state flux of 68.60 µg/h/cm²; flux was 2.58 times higher than that of conventional gel. In induced arthritis, AKBA nanoemulgel administration gradually decreased paw thickness and degree of arthritis. The treatment alleviated haematological abnormalities associated with the disease and decreased serum RF, CRP, TNF-α, IL-6 and IL-1β levels compared with the disease control group. Radiologically, joint architecture was conserved with lesser swelling and bone erosions of joints, while histopathologically, there was attenuation of cartilage erosion and synovitis. Conclusion: It was clear from the above results that the AKBA nanoemulgel increased transdermal penetration and sustained release of drug with significant anti-arthritic and anti-inflammatory activity in experimental rheumatoid arthritis. Therefore, it was concluded that AKBA nanoemulgel could be a useful transdermal approach for the treatment of rheumatoid arthritis.Background: Rheumatoid arthritis (RA) is an autoimmune condition that causes inflammation of the synovial membrane, leading to joint pain, swelling and destruction. 3-O-acetyl-11-keto-β-boswellic acid (AKBA), a constituent of Boswellia serrata, effective against inflammation and arthritis, but suffers from limited aqueous solubility and permeability through skin. In this regard, the objective of the current study was to prepare AKBA loaded nanoemulgel and explore its therapeutic potential in rheumatoid arthritis. Methods: An optimized AKBA nanoemulsion was added into gel matrix prepared with HPMC K15M and carbopol 940 to formulate nanoemulgels. These formulations were evaluated for physicochemical properties, in-vitro drug release and ex-vivo skin permeation. The optimized formulation was then tested in an arthritis animal model induced with complete freund’s adjuvant (CFA). Haematological, serological parameters were estimated and radiological, histopathological examination of ankle joints was also conducted. Results: Nanoemulgel formulation NG5 made of carbopol 940 was chosen as the optimized nanoemulgel in terms of physicochemical properties and drug release properties. NG5 had the following physical characteristics: pH of 6.11 ± 0.04, viscosity of 538.42 ± 2.84 cP and drug content of 105.12 ± 0.08%. The formulation had 93.42% drug diffusion cumulatively over 24 h. In ex-vivo permeation studies, cumulative permeation was found to be 1487.32 ± 8.46 µg/cm², with a steady state flux of 68.60 µg/h/cm²; flux was 2.58 times higher than that of conventional gel. In induced arthritis, AKBA nanoemulgel administration gradually decreased paw thickness and degree of arthritis. The treatment alleviated haematological abnormalities associated with the disease and decreased serum RF, CRP, TNF-α, IL-6 and IL-1β levels compared with the disease control group. Radiologically, joint architecture was conserved with lesser swelling and bone erosions of joints, while histopathologically, there was attenuation of cartilage erosion and synovitis. Conclusion: It was clear from the above results that the AKBA nanoemulgel increased transdermal penetration and sustained release of drug with significant anti-arthritic and anti-inflammatory activity in experimental rheumatoid arthritis. Therefore, it was concluded that AKBA nanoemulgel could be a useful transdermal approach for the treatment of rheumatoid arthritis.