Table 5.
In vivo proof of concept studies of nanoformulated compounds in melanoma murine models.
| Formulation/Compound (No/Name) | Animals (n) | Animal Model | Treatment (Dose) | Effects | Reference |
|---|---|---|---|---|---|
| F1/Cuphen | C57Bl/6 mice (5) | Syngeneic melanoma model (B16F10) | i.v., three-times a week, for 2 weeks (2.5 mg/kg) | Delay of tumor progression RTV = 8 versus 13 for free Cuphen and 24 for control |
[101] |
| F2/Bis-AO | C57BL/6J mice | Syngeneic melanoma model (B16F10) | i.v., five injections every alternate day | ↓ Tumor volume ↑ Survivability |
[52] |
| F3/Edelfosine | Athymic nude mice (4) | Syngeneic melanoma model (A375) | i.v. on days 9, 11, 13, 15 and 17 (20 mg/kg) | ↓ Melanoma tumor growth (169.5 ± 64.6 mm3 on day 30) ↑ Survival time (54 days versus 48 days of edelfosine in pegylated liposome) |
[53] |
| F4/Celecoxib + Plumbagin | Athymic-foxn1nu nude mice | Syngeneic melanoma model (UACC 903 or 1205 Lu) | i.v., alternate day, 3–4 weeks (15 + 1.5mg/kg) | Tumor inhibition up to 72% | [54] |
| F5/Plumbagin | C57BL/6J mice (8) | Syngeneic melanoma model (B16F10) | i.v., on days 1, 3, 5, 7 and 10 (2 mg/kg) | ↓ Tumor volume (VDT = 4.2 ± 0.7 for pegylated liposomes; 3.8 ± 0.6 for conventional liposomes versus 2.4 ± 0.2 for free plumbagin and 1.6 ± 0.4 for vehicle-treated animals) | [183] |
| F6/ATK | Athymic-foxn1nu nude mice (4) | Syngeneic melanoma model (UACC 903 or 1205 Lu) | i.v., daily, 3–4 weeks (30 and 40 mg/kg) | ↓ Melanoma tumor growth [58% (UACC 903) and 55% (1205 Lu)] | [56] |
| F7/3N-TPI | C57BL/6 mice | Metastatic model (B16F10) | 15 min, 5 and 10 days after tumor inoculation (0.4 and 2 mM) | ↓ Number of lung nodules, compared to vehicle control and free compound | [184] |
| F8/CKD-602 | NCR.nu/nu homozygous mice (5–12) | Syngeneic melanoma model (A375) | i.v., once weekly, twice weekly or once every 2 weeks, for 3 weeks (0.1 to 3.5 mg/kg) | CTR = ≥ 0.3 mg/kg (once weekly administration) MED = 0.15 mg/kg (once weekly), ≤ 0.3 mg/kg (twice weekly) and 0.1–0.3 mg/kg (every 2 weeks) versus ≤30 mg/kg for free form (once weekly) TI = 10 (once weekly), ~8 (twice weekly) and ~5 (every 2 weeks) versus >1 for free form (once weekly) |
[58] |
| F9/Leelamine | Athymic-foxn1nu nude mice (5) | Syngeneic melanoma model (UACC 903 or 1205 Lu) | i.v., daily, 3–4 weeks (30 mg/kg) | ↓ Tumor volume (~55%) | [189] |
| F10/Juglone | C57BL/6J mice | Syngeneic melanoma model (B16F1) | i.v. on days 1, 3 and 5 (1 mg/kg) | Delay tumor growth kinetic parameters (VDT = 3.6 ± 0.7 versus 2.9 ± 0.7 for free juglone and 1.6 ± 0.5 for vehicle control) ↑ Survival time (32 days versus 28 days for free julone and 19 days for vehicle control) |
[59] |
| F11/CytD | C57BL/6N mice (5) | Syngeneic melanoma model (B16) | i.v., every 3 days for 15 days (50 mg/kg) | Inhibition of tumor growth ↑ Survival time ↓ Average number of vessels per high-power field Inhibition of angiogenesis |
[60] |
Abbreviations: RTV: relative tumor volume; VDT: volume doubling time; MED: minimum efficacious dose; CTR: Complete tumor regression; TI: Therapeutic index—defined as the ratio of the maximum tolerated dose to the minimum efficacious dose.