Fig. 3: In vivo safety evaluation and in vivo drug release of CAB ISFIs in BALB/c mice.

a Local inflammation of excised depots and surrounding subcutaneous tissues collected at day 3, 7, and 30 post-injection (n = 3/timepoint for CAB ISFI treated mice and n = 1/timepoint for control (no injection) mice) and stained with H&E. Asterisks indicate CAB implant. Arrows indicate infiltrated immune cells and areas of inflammation. All scale bars represent 1 mm. b Inflammatory score of subcutaneous tissue surrounding the depot evaluated using a light microscope and scored blindly by a certified pathologist. Black bars represent the median inflammation score at each timepoint (n = 3 per timepoint). Inflammation scoring: 0: inflammatory cells present within expected limits; 1: minimal inflammation, few increased, scattered immune cells present; 2: mild inflammation, small clusters of immune cells to thin or localized tracks of inflammation or mild increase of the number of cells diffusely surrounding the depot; 3, moderate, thicker or multiple tracks of inflammation or moderate numbers of cells diffusely surrounding the depot; 4, severe, coalescing tracks of inflammation large enough to replace normal tissue architecture or severe numbers of cells diffusely surrounding the depot; 5, marked, inflammation present that is replacing expansive areas of normal tissue architecture. c Concentration of TNF-α (pg/mL) in plasma quantified by ELISA at day 3 (n = 3), 7 (n = 3), and 30 (n = 5) post-injection. d Concentration of IL-6 (pg/mL) in plasma quantified by ELISA at day 3 (n = 3), 7 (n = 3), and 30 (n = 5) post-injection. e CAB concentration (average ± standard deviation) in plasma (1215 mg/kg) for 90 days (n = 6 per timepoint). 1× and 4× PA-IC₉₀ values are indicated with dotted lines for CAB (166 ng/mL and 664 ng/mL, respectively). Plasma samples of individual mice are shown in Supplementary Fig. 7. Source data are provided as a Source Data file.