FIGURE 4.

In vivo efficacy of ND-L02-s0201 in silica-induced chronic lung fibrosis model in rats. a) Model illustration. Male Sprague-Dawley rats were treated with silica six times at 25 mg per g of lung (Day 0, 1, 2, 14, 28, and 42) to induce chronic lung damage. ND-L02-s0201 was dosed i.v. weekly or once every two weeks for 10 weeks. Lung hydroxyproline (HP) content (b, f and j), trichrome score (c, g and k), histology score (d, h and l) and relative lung weight (e, i and m) were performed as described in figure 1 following necropsy on respective days. b–e) Silica treated animals were monitored on Days 21, 35, 52, 73, and 101 to monitor lung damage progression. f–i) Three study durations were compared with termination on Days 52, 73, and 101 to evaluate ND-L02-s0201 efficacy. j–m) ND-L02-s0201 treatment were completed once every two weeks at 4, 2, and 1 mg·kg⁻¹ for five doses or with an initial dose at 2 mg·kg⁻¹ starting on Day 35 plus nine weekly follow up doses at 2, 1, and 0.5 mg·kg⁻¹. 4 × 5: 4 mg·kg⁻¹ for 5 doses; 2 × 5: 2 mg·kg⁻¹ for 5 doses; 1 × 5: 1 mg·kg⁻¹ for 5 doses; 2 × 10: 2 mg·kg⁻¹ for 10 weeks; 2 + 1 × 9: 2 mg·kg⁻¹ initial then 1 mg·kg⁻¹ for 9 weeks; 2 + 0.5 × 9: 2 mg·kg⁻¹ initial then 0.5 mg·kg⁻¹ for 9 weeks. Animal lungs were examined on Day 101 follow standard procedures described above. *: p<0.05; **: p<0.01; ***: p<0.001.