Table 3 Combination-based formulations studied in BC
Combination studied | Dose | Model | Formulation designed | Pharmacological effects | References |
|---|---|---|---|---|---|
Paclitaxel + Curcumin | Paclitaxel 0.1 M + Curcumin 1 µM at 37 °C for 24 h | MCF 7 cell lines | Liposomes | Improved chemotherapeutic efficiency was observed due to induced stronger G2/M arrest | [110] |
Doxorubicin + Curcumin | Curcumin50 mg/Kg + Doxorubicin 50 mg/ Kg Once a week for 7 weeks | BALB/c mice xenograft model (MCF- 7 cell lines injected) | Transferrin-decorated nanoparticles | Effective targeting, stronger antitumor effect and decreased cytotoxic effects of doxorubicin in bc xenograft mouse model | [111] |
Doxorubicin + Curcumin | Doxorubin 10 mg /kg (i.v) + Curcumin 10 mg/kg (i.v) injected every other 2 days for 12 days | Female Balb/C mice | Micellar delivery system | Better tumor targeting and accumulation of drugs. It even efficiently inhibited tumor growth It showed minimal damage to cardiac tissue compared to using doxorubicin alone due to the potential myocardial effect possessed by curcumin | [112] |
Vincristine + Quercetin | Vincristine 1.33 mg days/kg (two-thirds of the maximum tolerated dose in severe combined immunodeficiency disease (SCID) mice) + Quercetein 0.24 mg/kg. At these values, the molar ratio of vincristine/quercetin was 2:1 | SCID mice xenograft model (JIMT-1 cell lines injected) | Liposomes | Significant antitumor activity was observed even when two-thirds of the maximum tolerated dose of Vincristine was used | [36] |
Tamoxifen + Resveratrol | Tamoxifen 1.02 mg/kg (oral) and Resveratrol 10.20 mg/kg (oral) once | Albino Wistar rats | Self-nano emulsifying drug delivery system (SNEDDS) | The oral bioavailability of TAM from SNEDDS was significantly higher, being 1.63 times greater (p < 0.05) than the combination suspension and 4.16 times greater (p < 0.05) than the TAM suspension | [72] |
Doxorubicin + Berberine | Berberine (12 mg/ Kg) and Doxorubcin (1.2 mg/ Kg) for 16 days | Female BALB/c mice | Liposomes | Significant tumor growth inhibition in 4T1 murine mammary carcinoma compared to Doxil prevented the myocardial toxicity caused by Doxil | [113] |
Doxorubicin + Berberine | 25 µM + 25 µM incubated for 48 h | MDA-MB-231 and T47D cells | PLGA nanoparticles | The formulation demonstrated the excellent anti-proliferative effect compared to the individual drugs/bioactives against MDA-MB-231 and T47D cells | [114] |
Doxorubicin + Quercetin | 0.156 µg/mL + 40 µg/mL for 72 h | MCF 7 cell lines | PEGylated niosomes | The formulation exhibited higher toxicity against BC cells compared to the unencapsulated forms and showed a synergistic effect | [115] |
Docetaxel + Gemcitabine | Docetaxel 2 mg/Kg (i.v) + Gemcitabine 10 mg/Kg (i.v.) per day via tail vein for 7 days | Female Sprague Dawley Rats | Albumin nanoparticles | The AUC increased by 6.12 and 3.27-fold and T1/2 by 6.28 and 8.9-fold of docetaxel and gemcitabine as compared to Taxotere® and Gemzar® | [116] |
Pemetrexed + Ellagic acid | Pemetrexed 34 µg/mL + Ellagic acid 26 µg/mL for 24 h | MCF-7 cell lines | Mesoporous silica nanoparticles | The formulation demonstrated a sequential faster release of ellagic acid followed by a sustained release of pemetrexed It showed the highest cytotoxicity against MCF-7 BC cells, as revealed by the lowest combination index compared to free drugs | [117] |
Paclitaxel + Curcumin | Paclitaxel 13.54 µg/mL and Curcumin 44.60 µg/mL for 48 h Paclitaxel 30.75 µg/mL + Curcumin 76.71 µg/mL for 48 h | MCF-7 cell lines MCF- 10 A cell lines | PEGylated niosomes | The Curcumin and Paclitaxel IC50 value was reduced by threefold and 3.6-fold, respectively Combination formulation was effective in enhancing the cytotoxicity activity against MCF-7 cells | [118] |
Methotrexate + Curcumin | 5 mg Methotrexate (i.v) + 2.5 mg Curcumin (i.v.) both for 4 weeks | Sprague Dawley rats | PLGA nanoparticles | Co-delivery demonstrated a synergistic effect on inhibiting the progression of BC | [119] |
Paclitaxel + Doxorubicin + Cannabidiol | Paclitaxel 5.52 nM + Doxorubcin 0.03 µM + Cannabidiol 20 µM for 48 h Paclitaxel 22.86 nM + Doxorubcin 1.41 µM + Cannabidiol 10 µM for 48 h | MCF-7cell lines MDA-MB-231cell lines | Polymeric microparticles | A Significant reduction of the effective concentration of antineoplastic agents in MDA-MB-231 and MCF-7 cells was observed | [120] |
Guanidine + Curcumin | Guanidine 25 µM + Curcumin 30 µM for 72 h | MCF-7 Cell lines | Mesoporous silica nanoparticles | The formulation induced delayed apoptosis and necrosis at 48 and 72 h compared with individual-drug-treated cells An Increase in the phosphorylation of oncogenic proteins inducing cell death in MCF-7 cells was observed | [121] |