Because the therapeutic effects of rituximab is largely dependent on the Fc-related antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) [36], the Fab fragments demonstrated low cytotoxicity in both Raji and Daudi cells in all the tested concentrations (0.005 to 1.3 μg/mL), which corresponded to the ADR concentrations in the liposomal system. Furthermore, the half maximal (50%) inhibitory concentration (IC50) of ADR was calculated to evaluate the cytotoxicity of the liposomal drug delivery systems according to the ADR concentration dependence of Ilomastat cell line the cell viability
profile. It was shown in Figure 5C that PC-ADR-Fab demonstrated
the lowest IC50 to Raji (0.103 μg/mL) and Daudi (0.094 μg/mL) cells learn more compared with PC-ADR-BSA (IC50Raji 0.208 μg/mL, IC50Daudi 0.229 μg/mL) and free ADR agents (IC50Raji 0.436 μg/mL, IC50Daudi 0.441 μg/mL). Figure 5 In vitro antitumor activity of ADR loaded liposomes. Concentration-dependent cytotoxicity evaluation of free ADR, rituximab Fab, PC-ADR-BSA, and PC-ADR-Fab in Raji cells (A) and Daudi cells (B). (C) The IC50 to Raji and Daudi cells of free ADR, PC-ADR-BSA, and PC-ADR-Fab. Pharmacokinetics of ADR-containing liposomes in tumor bearing SCID mice After a short injection of free ADR and ADR-containing liposomes at 5 mg/kg into lymphoma-bearing BAY 11-7082 purchase SCID mice, the plasma ADR concentrations were measured at different time intervals. The data were analyzed using the PK solver software [32] and the results are all fitted to a trilocular pattern [37]. The time-concentration curve
is shown in Additional file 2: Figure S2 and the PK parameters in Table 2. As we can see, a remarkable difference in plasma PK was observed after the tail vein administration of free and liposomal ADR. The t 1/2γ (the elimination half time in the elimination phase) was relatively longer for irrad liposomes (34.53 ± 2.63 h) than that for non-irrad liposomes (21.13 ± 1.50 h) and free drugs (9.56 ± 4.06 h). In contrast, the clearance (CL) was significantly Sclareol reduced for irrad liposomes (6.63 ± 3.74 ml/h versus CLnon-irrad liposomes 8.82 ± 4.54 ml/h, CLfree drugs 30.96 ± 5.86 ml/h). Table 2 Tumor bearing nude mice serum pharmacokinetic parameters comparing free and liposomal ADRs ( n = 3) Parameter Unit Free ADR Non-irrad Irrad t 1/2α h 0.20 ± 0.02 0.19 ± 0.04 0.21 ± 0.05 t 1/2β h 0.98 ± 0.19 3.89 ± 0.79 1.57 ± 1.31 t 1/2γ h 9.56 ± 4.06 21.13 ± 1.50 34.53 ± 2.63 CL mL/h 30.96 ± 5.86 8.82 ± 4.54 6.63 ± 3.74 C max μg/mL 50.45 ± 5.54 54.13 ± 4.34 53.04 ± 5.68 AUC0-t (μg/mL) · h 79.97 ± 11.36 447.19 ± 54.19 713.49 ± 120.51 MRT h 6.37 ± 2.15 27.54 ± 1.53 48.58 ± 4.