Table 8.
Review of original articles assessing hemolysis induced by polymeric nanoparticles.
| Nanomaterial | Polymer characterization | Nanomaterial characterization | Testing method | Model | Dose/concentration range | Results | Observations | References |
|---|---|---|---|---|---|---|---|---|
| Chitosan NPs | 270 kDa | 367 nm +5 mV |
Erythrocyte incubation (2 h) | Human blood | 2000 μg/mL | Chitosan NPs were slightly hemolytic (~7%) | – | Shelma and Sharma, 2011 |
| Chitosan NPs | Low molecular weight chitosan ≥75% DD |
180 nm + 48 mV (acetic acid) 150 nm +39 mV (lactic acid) 140–160 nm +(20–25) mV (saline) |
Whole blood incubation (3 h) | Human blood | 50 μg/mL | NPs prepared in acetic acid medium showed high % hemolysis compared to those prepared in lactic acid medium, whereas the saline-dispersed NPs were found to be hemocompatible |
The authors also tested the molecular chitosan and was hemocompatible | Nadesh et al., 2013 |
| Chitosan NPs | Low molecular weight chitosan (85% DD) | ≤ 100 nm +40 mV |
Erythrocyte incubation (2 h) | Human blood | 50–300 μg/mL | No significant hemolysis | Bulk chitosan was tested at the same concentrations. | Sarangapani et al., 2018 |
| Chitosan NPs | 50 kDa and 85% DD | ~300 nm +35 mV |
Erythrocyte incubation (2, 4 h) | Wistar rat | 2.5 and 3.75 mg/mL | Low hemolysis rates | Kumar et al., 2017 | |
| Oleoyl-carboxymethyl-chitosan (OCMCS) nanoparticles | 170 kDa chitosan, 92.56% DD modified with chloroactic acid and oleoyl chloride | 171 nm +19 mV |
Erythrocyte incubation (30, 60 min) | Carp blood | 1 and 2 mg/mL | No hemolysis | Liu et al., 2013 | |
| PLA NPs | Poly(D,L-lactide) (PDLLA) 101782 g/mol and 0.68 dL/g | 188 nm −24 mV (water) 109 nm −7 mV (water) |
Whole blood incubation (3 h) | Human blood | 38, 50, 200, 250 μg/mL | No hemolysis | Da Silva et al., 2019 | |
| PLA NPs | Poly(D,L-lactide) (PDLLA) 101782 g/mol and 0.68 dL/g | 188 nm −24 mV (water) 109 nm −7 mV (water) |
Whole blood incubation (3 h) | Human blood | 75, 100, 300, 400 μg/mL | No hemolysis | Da Silva et al., 2019 | |
| Amphotericin loaded PEG-PLGA NPs | Copolymer produced with 6000 Da PLGA (lactic to glycolic acid molar ratio of 1:1) and 15% PEG | 25 nm | Erythrocyte incubation (8 and 24 h) | Sprague Dawley Rat blood | Equivalent to 20, 50, and 100 μg/mL of amphotericin | Low hemolysis rate (<15%) Concentration dependent |
Reduced hemolysis when compared to amphotericin commercial formulation (same dose) | Radwan et al., 2017a |
| Amphotericin loaded PEG-PLGA NPs | PLGA lactic to glycolic acid 50:50 with 40–75 KDa and PEG with 10 KDa | 170 nm | Erythrocyte incubation (1 h) | Human blood | Equivalent to 25 μg/mL of amphotericin | Nanoparticles reduced the hemolytic activity of amphotericin in more than 95% Blank nanoparticles induced negligible hemolysis (unknown concentration) |
Moraes Moreira Carraro et al., 2017 | |
| Amphotericin loaded PLGA NPs | PLGA lactic to glycolic acid 50:50 with 40–75 KDa | 190 nm | Erythrocyte incubation (1 h) | Human blood | Equivalent to 25 μg/mL of amphotericin | Nanoparticles reduced the hemolytic activity of amphotericin in more than 95% Blank nanoparticles induced negligible hemolysis (unknown concentration) |
Moraes Moreira Carraro et al., 2017 | |
| Casein stabilized PLGA NPs | PLGA lactic to glycolic acid 75:25, 5,000 kDa PEI: 25 kDa |
165 nm −21 mV |
Diluted whole blood incubation (3 h) | Human blood | 0.01–10 mg/mL | No hemolysis | Pillai et al., 2015 | |
| PVA stabilized PLGA NPs | PLGA lactic to glycolic acid 75:25, 5,000 kDa PEI: 25 kDa |
159 nm −0.14 mV |
Diluted whole blood incubation (3 h) | Human blood | 0.01–10 mg/mL | No hemolysis | Pillai et al., 2015 | |
| PEI stabilized PLGA NPs | PLGA lactic to glycolic acid 75:25, 5,000 kDa PEI: 25 kDa |
158 nm +30 mV |
Diluted whole blood incubation (3 h) | Human blood | 0.01–10 mg/mL | 7% hemolysis at the highest concentration tested (10 mg/ml) | Pillai et al., 2015 | |
| Acyclovir loaded Galactosylated (Gal)-PLGA NPs | na | 173 nm −20 mV |
Erythrocyte incubation (3 h) | na | 0.1 mM of acyclovir | 3.3% hemolysis | Free acyclovir in the same concentration induced 16.7% hemolysis | Gupta et al., 2012 |
| Acyclovir loaded PLGA NPs | na | 198 nm −8.5 mV |
Erythrocyte incubation (3 h) | na | 0.1 mM of acyclovir | 9.8% hemolysis | Free acyclovir in the same concentration induced 16.7% hemolysis | Gupta et al., 2012 |
| Poly(lactic-co-glycolic acid) (PLGA)–polyethylene glycol (PEG)–folic acid (FA) NPs | PEG – MW 2kDa PLGA – MW 90 kDa (lactic to glycolic acid 50:50), carboxyl-terminated |
131 nm −25 mV |
Diluted whole blood incubation (1 h) | New Zeeland Rabbit blood | 0.033, 0.05, and 0.1 mg/mL | No significant hemolysis (<4%) | Chen et al., 2017 | |
| Poly(lactic-co-glycolic acid) (PLGA) NPs | PEG – MW 2 kDa PLGA – MW 90 kDa (lactic to glycolic acid 50:50), carboxyl-terminated |
83 nm −27 mV |
Diluted whole blood incubation (1 h) | New Zeeland Rabbit blood | 0.033, 0.05, and 0.1 mg/mL | No significant hemolysis (<4%) | Chen et al., 2017 | |
| Danorubicin loaded polyethylene glycol-poly L-lysine-poly lactic-co-glycolic acid (PEG-PLL-PLGA) NPs | na | 229 nm −20 mV |
Erythrocyte incubation (15 min−3 h) | New Zeeland Rabibit blood | 50 mg/mL (unloaded) | No hemolysis | Guo et al., 2015 | |
| Tamoxifen loaded PLA NPs | 85–160 kDa PLA | 155 nm −21.7 mV |
Erythrocyte incubation (4, 12, 24,48, 72, 96 h) | Human blood | 4.4 or 1.1 μM of tamoxifen | Negligible hemolysis at both concentrations and all incubations times | No results presented for blank NPs but is stated they cause no cellular damage to erythrocytes | Altmeyer et al., 2016 |
| Itraconazole loaded PLA NPs | PLA (molecular weight: 56,000 | 284 nm ~0 mV |
Erythrocyte incubation (3 h) | Wistar rat blood | 5–20 μg/mL of ITZ i.e., 53–212 μg/mL of NPs | Significant hemolysis (>5%), concentration dependent | Reduced hemolysis when compared to free itraconazol (same dose). Hemolysis is suggested to be caused by the drug release during incubation | Essa et al., 2012 |
| Itraconazole loaded PEG-PLA NPs | PEG7%-g-PLA, molecular weight: 8,300 | 197 nm ~0 mV |
Erythrocyte incubation (3 h) | Wistar rat blood | 5–20 μg/mL of ITZ i.e., 35–142 μg/mL of NPs | Significant hemolysis (>5%), concentration dependent | Reduced hemolysis when compared to free itraconazol (same dose). Hemolysis is suggested to be caused by the drug release during incubation | Essa et al., 2012 |
| Itraconazole loaded PEG-PLA NPs | [PLA–PEG–PLA]n, molecular weight: 3,900 | 185 nm ~0 mV |
Erythrocyte incubation (3 h) | Wistar rat blood | 5–20 μg/mL of ITZ i.e., 40–159 μg/mL of NPs | Significant hemolysis (>5%), concentration dependent | Reduced hemolysis when compared to free itraconazol (same dose). Hemolysis is suggested to be caused by the drug release during incubation | Essa et al., 2012 |
| Paclitaxel loaded monomethoxypoly (ethylene glycol)-b-poly(lactic acid) (mPEG-PLA) polymeric micelles |
mPEG-PLA copolymer (40/60) with a number average molecular weight of 4488.4 and mPEG-PLA copolymer (50/50) | (40/60): 37 nm After incubation with BSA: 40 nm (50/50): 44 nm After ncubation with BSA: 71 nm |
Erythrocyte incubation (1 h) | New Zeeland rabbit blood | 2–10% | Minimal hemolysis (<6%) | The toxicity of paclitaxel loaded mPEG-PLA (40/60) polymeric micelles was significantly lower than those of mPEG-PLA (50/50) | Li et al., 2014 |