In Vivo Quantitative Measurement of Arthritis Activity Based on Hydrophobically Modified Glycol Chitosan in Inflammatory Arthritis: More Active than Passive Accumulation

Abstract

We demonstrated that arthritis could be visualized noninvasively using hydrophobically modified glycol chitosan nanoparticles labeled with Cy5.5 (HGC-Cy5.5) and an optical imaging system. Activated macrophages expressing Mac-1 molecules effectively phagocytosed HGC-Cy5.5, which formed spherical nanoparticles under physiologic conditions. We estimated the applicability of HGC-Cy5.5 to quantitative analysis of arthritis development and progression. Near-infrared fluorescence images, captured after HGC-Cy5.5 injection in mice with collagen-induced arthritis, showed stronger fluorescence intensity in the active arthritis group than in the nonarthritis group. According to the progression of arthritis in both collagen-induced arthritis and collagen antibody-induced arthritis models, total photon counts (TPCs) increased in parallel with the clinical arthritis index. Quantitative analysis of fluorescence after treatment with methotrexate showed a significant decrease in TPC in a dose-dependent manner. Histologic evaluation confirmed that the mechanism underlying selective accumulation of HGC-Cy5.5 within synovitis tissues included enhanced phagocytosis of the probe by Mac-1-expressing macrophages as well as enhanced permeability through leaky vessels. These results suggest that optical imaging of arthritis using HGC-Cy5.5 can provide an objective measurement of disease activity and, at the same time, therapeutic responses in rheumatoid arthritis.

Stealth Nanogels of Histinylated Poly Ethyleneimine for Sustained Delivery of Methotrexate in Collagen-Induced Arthritis Model

“…Although LPS model is a bacterial toxin-induced arthritis that resembles pyogenic arthritis (27) and it differs from the CIA model which is routinely used for pharmacological screening, the advantage of this model over CIA for animal imaging is that the opposite ankle joint could be used as an internal control to show preferential accumulation of the nanogels in the inflamed vs. normal paw, thus demonstrating the effectiveness of the nanogel. The calculated enhancement ratio in inflamed joints increased moderately to about 2.7 whitin 1 h and then remained nearly unchanged until 4 h. The enhancement ratio is more than the minimal acceptable value of 1.5 and the reported value of 2.3 for the hydrophobically modified glycol chitosan nanoparticles (52). This accumulation of the nanogels might be due to nonspecific phagocytosis by activated macrophages, or due to the nanogels localized at the interstitial space because of increased permeability and retention effect at the inflamed tissues (5).…”

Rutin-loaded chitosan microspheres: Characterization and evaluation of the anti-inflammatory activity

“…The integration of the drug in the polymeric matrix provided a significant retention of the bioactive and induced a controlled drug leakage for up to 24 h. The extreme biocompatibility of chitosan evidenced no toxicity at the drug concentration used. All together these findings evidence the possibility for application of rutinloaded chitosan microspheres in the treatment of mucosa inflammation, such as in the synovial, lung and bowel compartments (Park et al, 2012;Soliman, Zhang, Merle, Cerruti, & Barralet, 2014;Gaspar et al, 2015). Moreover, the association of different anti-inflammatory active compounds with rutin in the same microformulation could generate innovative medicines suitable for treating acute inflammation, thus avoiding the need for massive drug concentrations and decreasing side effects.…”

Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis

“…A murine CIA model was established as previously described with minor modifications [ 29 ]. This model of arthritis in mice has been in use for over 30 years [ 30 , 31 ].…”