Administration of nanoparticles to K/BxN mice prior to onset of arthritis delayed disease. (A) Strategy for treating K/BxN mice with one, two, or five doses of nanoparticles prophylactically. PLGA-R nanoparticles contained 100 μg of rapamycin. (B-D) K/BxN mice, 21–25 days of age, were left untreated or treated once (x1) or weekly (every 6–7 days) for 2 (x2) or 5 (x5) consecutive weeks. Joint measurements were performed three times a week, and mice were considered to be at the study endpoint when one or more joint(s) measured 4 mm. Results over time for each group (n = 6–26), are shown as percent of mice with no joint swelling over 4 mm. Results are representative of two experiments. To facilitate comparisons, results for untreated mice and GPI-LP-CD22L (GPI-STALs) + PLGA-R are shown in panels B-D and C-D, respectively. (E) Disease severity assessed as total joint thickness for all four paws in treated mice out to 77 days. Statistical analyses were performed using a log-rank test in B-D and by two-way ANOVA with Tukey’s post-test in E (**** P ≤ 0.0001; *** P ≤ 0.001; ** P ≤ 0.01; *P ≤ 0.05 and ns indicates not significant).