Table 6.
Micellar formulations with salinomycin.
| Composition | Combination Therapy | Preparation Method | Size (nm) | PDI | Zeta Potential (mV) | EE (%) | Drug Loading (%) | In Vitro Release | Biological Effect | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| DSPE-PEG2000, conjugated with iRGD | - | Lipid film method | 14.0/13.7 1 | 0.24/0.31 1 | −17.7/−17.1 1 | 96.6/93.4 1 | 9.1/8.9 1 | 80% in PBS pH 5.5 + 0.1% SDS and 60% in PBS 7.4 + 0.1% SDS, at 48 h | Increased cytotoxicity against HepG2 cells and tumorspheres, compared to untargeted NPs and free Sali, respectively; superior penetration in tumor and efficacy in liver cancer-bearing mice | [48] |
| PEG-ceramide | - | Lipid film method | 14.6 | 0.25 | −4.4 | 76.7 | 6.3 | 75% in PBS pH 5.0 + 0.1% SDS and 50% in PBS pH 7.4 + 0.1% SDS, at 12 h | Synergistic effects of Sali and PEG-ceramide at 1:4 molar ratio; 4.5 and 2-fold increase in cytotoxicity in HepG2 cells and tumorspheres, compared to free Sali, at 48 h; increased apoptosis in HepG2 cells, but not in tumorspheres, compared to Sali; good safety profile and higher tumor growth inhibitory effects in vivo, compared to Sali | [50] |
| DSPE-PEG2000 | LA-SN38 prodrug 2 | Injection method | 61.7 | n.r. | n.r. | 97.24/99.98 3 | 32.71/33.64 3 | 80%/70% in PBS pH 7.4 + 0.1% Tween 80, at 96 h 3 | Synergistic effect; Sali reduced the IC50 of SN38 in HCC; stronger apoptotic effect in HCC cells, compared to free Sali and SN38 prodrug NPs; increased anti-CSC effect and decreased migration and invasion of HCC cells, compared to Sali; significant decrease in tumor volume in vivo, compared to Sali | [52] |
| DSPE-PEG2000 | MTX 4 | Lipid film method | 21.8 | 0.15 | −21.2 | 83.1/85.7 5 | 9.0/5.4 5 | 85% in PBS pH 5.5 and 70% in PBS pH 7.4, at 48 h/20% in PBS pH 5.5 and PBS pH 7.4, at 48 h 5; protease-dependent release profile | Enhanced inhibitory effects against HNSCC CSCs and in tumor-bearing mice, compared to single-loaded NPs and free drugs; significant reduction in toxicity of free drugs in mice | [89] |
| PLA-PEG2000 | - | Nanoprecipitation method and film hydration method | 127.1/154.5 6 | 0.22 7 | n.r. | 85.6–90.2 7 | 4.8–8.7 8 | 90% in PBS pH 7.4 + 0.5% SDS, at 48 h | Significant toxicity in AsPC-1 cells and tumor inhibition, but similar to free Sali; higher survival probability in tumor-bearing mice | [91] |
| DSPE-PEG2000, conjugated with EGFR aptamer | - | Lipid film method | 22.4/24.3 9 | 0.16/0.18 9 | −19.5/−19.7 9 | 82.1/80.3 9 | 10.4/9.7 9 | 70% in PBS and 80% in PBS + 10% FBS, after 72 h | Increased cell penetration and cytotoxicity of micellar Sali in lung cancer cells and CSCs, compared to free Sali; higher antitumor efficacy of EGFR-targeted micelles in vivo, compared to untargeted NPs and free Sali | [93] |
| PCL-PEG | PTX 10 | Film hydration method | 27.21 | 0.13 | n.r. | 99.78 | n.r. | 97.9% in PBS + 0.5% SDS, at 24 h | Micellar Sali effectively suppressed breast CSCs in vitro and in vivo; Sali sensitized PTX against MCF-7 cells; the combination of micellar Sali and Oct-modified PTX-NPs was more effective in vivo, compared to the single drug NPs or combined free drug treatments | [94] |
| Pluronic F127 | - | Film hydration method | 26 11 | 0.22 11 | −10.7 11 | 97.9 11 | n.r. | n.r. | No statistical difference in cytotoxicity against A549 cells between micellar Sali and free Sali; significant reduction in cell migration of A549 cells, compared to free Sali; time- and dose-dependent effect on P-gp expression; higher antibacterial activity towards MRSA than free Sali | [95] |
PDI, polydispersity index; EE, entrapment efficiency; DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000); SDS, sodium dodecyl sulfate; NP, nanoparticle; Sali, salinomycin; PEG, polyethylene glycol; LA-SN38, linoleic acid conjugated (7-ethyl-10-hydroxycamptothecin); n.r., not reported; HCC, hepatocellular carcinoma; CSC, cancer stem cell; MTX, methotrexate; HNSCC, head and neck squamous cell carcinoma; PLA, poly(lactic acid); EGFR, epidermal growth factor receptor; FBS, fetal bovine serum; PCL, polycaprolactone; PTX, paclitaxel; Oct, octreotide; SDS, sodium salicylate; P-gp, P-glycoprotein; MRSA, methicillin-resistant Staphylococcus aureus. 1 Data reported for unconjugated and iRGD-conjugated salinomycin-loaded micelles, respectively. 2 Salinomycin and SN38 prodrug were co-loaded in the micelles; SN38 was formulated as linoleic acid-SN38 prodrug nanoparticles. 3 Data reported for salinomycin and SN38 prodrug, respectively. 4 Methotrexate and salinomycin were co-loaded in the micelles; methotrexate was conjugated to DSPE-PEG2000. 5 Data reported for salinomycin and methotrexate, respectively. 6 Data reported for the nanoprecipitation method, for drug to polymer ratios of 5% and 10%, respectively. 7 Data reported for micelles obtained by the nanoprecipitation method, with a drug to polymer ratio of 10%. 8 Data reported for the nanoprecipitation and film hydration methods, and for different drug to polymer ratios (5% and 10%). 9 Data reported for unconjugated and EGFR aptamer-conjugated salinomycin-loaded micelles, respectively. 10 Paclitaxel was loaded in octreotide-modified PCL-PEG micelles, separately from salinomycin. 11 Data reported for the optimal formulation of salinomycin-loaded micelles.