Table 2.
Examples of NP-based combination chemotherapy in chronic diseases in mice, rats, primates and humans.
| Drug combinationa (Log P) | Drug ratio (w/w)b | NP composition | NP size (nm)c | Disease state | References |
|---|---|---|---|---|---|
| Human studies | |||||
| Cytarabine (−2.8), Daunorubicin HCl (1.83) | ~2.27/1 | DSPC, DSPG, cholesterol | 100 ± 20 | Acute myeloid leukaemia | [48,74] |
| Floxuridine (−1.16), Irinotecan HCl (3.2) | ~1/2.75 | DSPC, DSPG, cholesterol | 100 ± 20 | Colorectal cancer | [48,49] |
| Primate studies | |||||
| Lopinavir (5.94), Ritonavir (4.24), Tenofovir (−1.6) | 1/1/0.5 | DSPC, DSPE-mPEG2000 | ~52 | HIV/AIDS | [53,57] |
| Rat studies | |||||
| Cisplatin (−2.19), Docetaxel (2.4) | 2/1 | Poly(l-glutamic acid)-PEG | 28 ± 9 | Melanoma | [75] |
| Doxorubicin HCl (1.27), Gemcitabine (−1.4) | 1/1.12 | HPMA | 23.5 kDa | Prostate carcinoma | [76] |
| Mouse studies | |||||
| 10-hydroxycamptothecin (1.69), Doxorubicin HCl (1.27) | 1/1.24 | PBA-PEG-ss-PCL | 143 ± 3 | Breast cancer, lung metastasis | [77] |
| 5-Fluorouracil (−0.89), Oxaliplatin (−0.47) | 5/1 | PLA | ~300 | Colorectal cancer | [78] |
| 5-Fluorouracil (−0.89), Paciltaxel (3.0) | 3.75/1 | Vitamin E, TPGS | 82 | Cervical cancer | [79] |
| Axitinib (4.56), Celastrol (5.9) | N/A | Mesoporous silica, DSPE-mPEG2000 | 120 | Squamous carcinoma | [80] |
| BLZ-945 (3.4), Cisplatin (−2.19) | 2.5/1 | PEG-b-PAEMA-PAMAM | ~90 | Breast cancer and metastasis | [81] |
| Cisplatin (−2.19), Doxorubicin HCl (1.27) | 1/1 | PAA | ~100 | Breast cancer | [82] |
| Cisplatin (−2.19), Gemcitabine monophosphate (−0.12) | 1/5.8 | DOPA, PLGA-PEG | ~120 | Bladder cancer | [50] |
| Cisplatin (−2.19), Paclitaxel (3.0) | 3.78/1 | PEG, poly(l-Glu), poly(l-Phe) | 95 ± 3 | Ovarian cancer | [83] |
| Cisplatin (−2.19), Paclitaxel (3.0) | 2/1 | PEG5K(COOH)8-L-CA8 | 16.9 ± 4.8 | Lymphoma, ovarian cancer | [84] |
| Cisplatin (−2.19), Rapamycin (4.3) | 2/1 | PLGA-PEG-MBA, DOPA | 80 | Melanoma | [51] |
| Camptothecin (1.74), Doxorubicin HCl (1.27), Oxaliplatin (−0.47) | 3/2/5 | PC and PEG macromonomers | 21 ± 6 | Ovarian cancer | [85] |
| Combretastatin-A4 (3.7), Doxorubicin (1.27) | 100/1 | PLGA, PC, DSPE-PEG-2000, cholesterol | 180–200 | Melanoma, Lewis lung carcinoma | [86] |
| Combretastatin-A4 (3.7), Doxorubicin HCl (1.27) | 1/4 | DSPE-PEG5000, oleic acid, Fe3O4 | 53.7 ± 5.3 | Breast cancer | [87] |
| Combretastatin-A4 (3.7), Methotrexate (−1.85) | 1/1.67 | Pullulan | 200–250 | Hepatocellular carcinoma | [88] |
| Combretastatin-A4 (3.7), Paclitaxel (3.0) | 4/1 | PLGA | 244.1 ± 4.3 | Melanoma | [89] |
| Combretastatin-A4 (3.7), Paclitaxel (3.0) | 4/1 | mPEG2000-PLA2000 | 68.3 ± 1.4 | Lewis lung carcinoma, melanoma liver metastasis | [90] |
| Dasatinib (1.8), Doxorubicin HCl (1.27) | 3.37/1 | POEG | 200.8 | Breast cancer | [91] |
| Daunorubicin (1.83), Oxaliplatin (−0.47) | 1/2 | MPEG-P(LA-co-MCC) | 208 | Hepatocarcinoma | [92] |
| Diclofenac (4.51), Docetaxel (2.4) | 1.34/1 | PLGA, DPPC, DSPE-PEG2000 | 155.7 ± 1.2 | Glioblastoma | [93] |
| Docetaxel (2.4), Doxorubicin HCl (1.27) | 3.24/1 | PBS/PBDL, HPMA | 122 | T-cell lymphoma | [94] |
| Docetaxel (2.4), Mertansine (2.2) | 1/1.7 | PEG-TMC | 49 | Melanoma | [95] |
| Doxorubicin HCl (1.27), Paclitaxel (3.0) | 1/1 | DOPC, DOPG, MPB | 220 | Breast cancer | [96] |
| Gemcitabine (−1.4), Oxaliplatin (−0.47) | 1/2.5 | DOPA, DOPC, DSPE-PEG2000, cholesterol | 49.5 ± 0.6 | Pancreatic cancer | [97] |
| Irinotecan (3.2), Oxaliplatin (−0.47) | 1.5/1 | Egg PC, cholesterol | 194.6 ± 4.0 | Colorectal cancer | [98] |
| Irinotecan (3.2), Oxaliplatin (−0.47) | 2.5/1 | DPPC, triglyceride, Oleic acid, and Pluronic F68 | 126.9 ± 2.7 | Colorectal cancer | [99] |
| Lonidamine (4.3), Paclitaxel (3.0) | 4/1 | PCL, PLGA-PEG | 120–160 | Breast cancer | [100] |
| Paclitaxel (3.0), Rapamycin (4.3) | 1/3 | PEG-PCL | 9.2 ± 3.8 | Breast cancer | [52] |
| Paclitaxel (3.0), Tamoxifen (7.1) | 1/2 | PEO-PCL | 100–300 | Ovarian adenocarcinoma | [101] |
| Quercetin (1.5), Sorafenib (3.8) | 1.26/1 | DSPE-PEG2000, PLGA | 136.5 ± 3.2 | Hepatocellular carcinoma | [77] |
| Quercetin (1.5), Topotecan (0.8) | 1/1.5 | Mesoporous silica, PAA-chitosan | 72.9 | Breast cancer | [102] |
a
LogP values are included in brackets. The values are obtained from Drugbank.com or Pubchem.com. Computed values are used where experimental values are not available.
b
Drug ratios are obtained from authors’ claims if available or by calculating dosages of their in vivo administrations. Some studies investigated several ratios. The ratios in this table were used in in vivo studies.
c
NP size values are hydrodynamic size or EM size, or molecular weight where specified.