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. 2020 Oct 9;15:7719–7743. doi: 10.2147/IJN.S267424

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© 2020 Pangeni et al.

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In vivo analyses of the inhibitory effects of the following on tumor growth in CT26 tumor-bearing mice: biweekly intravenous administration of 3.3 mg/kg OP [OP-IV (3.3)] and 10 mg/kg OP [OP-IV (10)]; once-daily oral administration of 10 mg/kg OP in aqueous solution (OP-S); once-daily oral administration of ODSF as 2.5 mg/kg OP [ODSF (2.5)]; once-daily oral administration of ODSF as 10 mg/kg OP [ODSF (10)]; and once-daily oral administration of ODSF as 20 mg/kg OP [ODSF (20)], for 21 days. (A) Tumor volumes in mice [^aP< 0.05, ^bP<0.01, ^cP<0.001 compared to the control. ^dP<0.01, ^eP<0.001 compared to OP-IV (3.3). ^fP<0.05, ^gP<0.01 compared to OP-IV (10). ^hP<0.001 compared to OP-S (10). ⁱP<0.001 compared to ODSF (2.5)]. (B) Photographs of tumors isolated from each group on day 21. Scale bar: 10 mm. (C) Tumor weights in CT26 tumor-bearing mice on day 21 [^aP<0.05, ^bP<0.001 compared to the control. ^cP<0.05 compared to OP-IV (10). ^dP<0.05 compared to OP-S (10). ^eP<0.05 compared to ODSF (2.5)]. (D) Changes in mouse body weights during treatment [^aP<0.05, ^bP<0.001 compared to the control. ^cP<0.001 compared to OP-IV (3.3). ^dP<0.01, ^eP<0.001 compared to OP-IV (10). ^fP<0.01, ^gP<0.001 compared to OP-S (10). ^hP<0.001 compared to ODSF (2.5). ⁱP<0.05 compared to ODSF (10)]. (E) Representative cross-sectional images of isolated tumor tissues obtained 21 days after various treatments, stained as follows: With anti-CD31 antibody, indicating microvessels (brown); anti-proliferating cell nuclear antigen (PCNA) antibody, indicating proliferating cells (brown); and via fluorescent terminal deoxynucleotidyl transferase-mediated dUPT nick-end labeling (TUNEL), indicating apoptosis (green fluorescence). Scale bars: 50 μm for anti-CD31 antibody and anti-PCNA antibody staining; 20 μm for TUNEL staining.

Notes: Statistics: one-way ANOVA followed by the Tukey multiple comparisons test. Each value is mean±standard error of the mean (n=14/group).

Abbreviations: OP, oxaliplatin; IV, intravenous; OP-S, OP in aqueous solution; DLM, N^α-deoxycholyl-l-lysyl-methylester; OP/DLM, ion-pairing complex between OP and DLM; P188, poloxamer 188; ODSF, solid oral formulation of OP/DLM with P188 and Labrasol.