Figures & data
Figure 1 Schematic representation of the structure of CDP-MP, a conjugate of a glycinate derivative of α-methylprednisolone (MP) and a cyclodextrin polymer (CDP). m Number of ethylene glycol repeating units (average m = 77 for PEG with Mw 3,400); n number of repeating units of CDP-MP (average n = 24 ± 5 for parent polymer Mw of 117 kDa).
Table 1 In vivo assay of CDP-MPTable Footnotea
Table 2 Comparison in particle size of CDP after MP loading and drug releaseTable Footnotea (n = 5)
Figure 2 Release kinetics of MP from the conjugates in PBS (pH 7.4) and human plasma (pH 7.4) at 37 °C over 3 days.
Table 3 Calculated IC50 values for the stimulation index in human lymphocytes for MP and conjugated MP (μg/ml in MP equivalents)Table Footnotea (n = 3)
Figure 3 Arthritis score by a standardized method (ranges 0 to 4). After combining scores for all paws, the maximum possible score is 16. Mean arthritis score (n = 5) is shown except for low doses of MP alone (0.01 and 0.1 mg/kg/day). Arthritis scores for these groups were similar to control animals (data not shown). Standard error of the mean (SEM) of arthritis scores is shown only for control vs. treatments that were significantly effective (p < 0.05).
Figure 4 Change in dorsoplantar swelling. CDP-MP at 0.7 and 7 mg/kg show significant reduction in dorsoplantar swelling. Mean dorsoplantar swelling (n = 5) is shown except for low doses of MP alone (0.01 and 0.1 mg/kg/day). Dorsoplantar swelling for these groups was similar to control animals (data not shown). SEM of dorsoplantar swelling is shown only for control vs. treatments that were significantly effective (p < 0.05).
Figure 5 Histology photomicrographs of Hematoxylin and Eosin stained joints of mice with collagen induced arthritis. A. Vehicle control with diffuse synovitis and bone destruction. B. CDP with scattered synovitis and bone resorption. C. Free MP (0.01 mg/kg/day) with moderate synovitis and full thickness bone defect. D. Free MP (0.1 mg/kg/day) with diffuse synovitis and bone resorption. E. CDP-MP (0.7 mg/kg/week) with sparse synovitis and small area of bone resorption F. CDP-MP (7 mg/kg/week) with scattered synovitis and small area of bone resorption.
Figure 6 Histological scores of synovitis, pannus and architecture. CDP-MP at 7 mg/kg/week shows significant improvement in all parameters such as synovitis, pannus and architecture compared to untreated controls (p < 0.04). Mean ± SEM (n = 5) is shown.
