Figure 7.
Encapsulation of drug into nanoparticles reduces toxicity associated with combination therapy. (A) Histogram depicting weight variation in SU-DHL-6 xenografts in different treatment groups on day 15 relative to day 0 of treatment: vehicle, venetoclax (100 mg/kg orally 5 times per week), S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week), combinations of venetoclax (100 mg/kg orally 5 times per week) and S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week) for 2 weeks (n = 4 or 5 mice). (B-E) Analysis of the effect of combination therapy on RBCs (B), platelets (C), hemoglobin (D), and WBCs (E) on day 15 of treatment. Mean and SD from 5 different mice per group. Treatment groups include vehicle, venetoclax (100 mg/kg orally 5 times per week), S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week) and combinations of venetoclax (100 mg/kg orally 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week). (F) Histogram depicting weight variation in SU-DHL-6 xenografts in different treatment groups on day 17 relative to day 0 of treatment: vehicle, S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), and venetoclax (25 mg/kg IV 3 times per week), combinations of S63845 (12.5 mg/kg IV 3 times per week) and venetoclax (25 mg/kg orally 3 times per week), and venetoclax-NP (25 mg/kg IV 3 times per week), and S63845 (25 mg/kg IV 5 times per week) plus venetoclax (100 mg/kg orally 5 times per week) for 2 weeks. (G-J) Analysis of the effect of combination therapy on RBCs (G), platelets (H), hemoglobin (I), and WBCs (J) on day 15 of treatment. Treatment groups include vehicle, S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), and venetoclax (25 mg/kg IV 3 times per week), combinations of S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), and venetoclax-NP (25 mg/kg IV 3 times per week). For weight loss, 2-way ANOVA was used and for hematologic toxicity, 1-way ANOVA was used to determine statistical significance between first day of treatment and subsequent time points. ***P < .001; **P < .01; *P < .05.

Encapsulation of drug into nanoparticles reduces toxicity associated with combination therapy. (A) Histogram depicting weight variation in SU-DHL-6 xenografts in different treatment groups on day 15 relative to day 0 of treatment: vehicle, venetoclax (100 mg/kg orally 5 times per week), S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week), combinations of venetoclax (100 mg/kg orally 5 times per week) and S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week) for 2 weeks (n = 4 or 5 mice). (B-E) Analysis of the effect of combination therapy on RBCs (B), platelets (C), hemoglobin (D), and WBCs (E) on day 15 of treatment. Mean and SD from 5 different mice per group. Treatment groups include vehicle, venetoclax (100 mg/kg orally 5 times per week), S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week) and combinations of venetoclax (100 mg/kg orally 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week). (F) Histogram depicting weight variation in SU-DHL-6 xenografts in different treatment groups on day 17 relative to day 0 of treatment: vehicle, S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), and venetoclax (25 mg/kg IV 3 times per week), combinations of S63845 (12.5 mg/kg IV 3 times per week) and venetoclax (25 mg/kg orally 3 times per week), and venetoclax-NP (25 mg/kg IV 3 times per week), and S63845 (25 mg/kg IV 5 times per week) plus venetoclax (100 mg/kg orally 5 times per week) for 2 weeks. (G-J) Analysis of the effect of combination therapy on RBCs (G), platelets (H), hemoglobin (I), and WBCs (J) on day 15 of treatment. Treatment groups include vehicle, S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), and venetoclax (25 mg/kg IV 3 times per week), combinations of S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), and venetoclax-NP (25 mg/kg IV 3 times per week). For weight loss, 2-way ANOVA was used and for hematologic toxicity, 1-way ANOVA was used to determine statistical significance between first day of treatment and subsequent time points. ***P < .001; **P < .01; *P < .05.

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