Table 1.
Summary of polymeric nanoparticle use for enhanced CNS drug delivery.
| Approach | Nanoparticle properties | Targeting | In vivo efficacy | Ref | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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| Core polymer |
Linkage | Surface coating |
Size (nm) |
PDI/ GSD |
Z-Pot. (mV) |
Payload | Encap. % |
Ligand | Amt. | Admin Route |
Dosage (mg/kg) |
Response | ||
| Receptor | PBCA | Acrylate | PS80 | 230 | NA | NA | Dalargin | 30 (S) | NA | NA | i.v. | 7.5 | 42.5 (28.9) % MPE | 18 |
| Receptor | PBCA | Acrylate | PS20 | 230 | 0.1 | NA | Dalargin | 30 (S) | NA | NA | i.v. | 10 | 7 | 20 |
| PS40 | 85.2 (20.7) % MPE | 7.4 (25.9) % MPE | ||||||||||||
| PS80 | 97.7 (4.6) % MPE | |||||||||||||
| C40 | 17.9 (16) % MPE | |||||||||||||
| Receptor | PBCA | Acrylate | PS80 | 270 | NA | NA | Doxorubicin | 80 (S) | NA | NA | i.v. | 5 | 6 μg/g | 21 |
| Receptor | PBCA | Acrylate | PS80 | 270 | 1.07 | NA | Doxorubicin | 70 (S) | NA | NA | i.v. | 3 × 2.5 | 43 % IST | 22 |
| Receptor | PBCA | Acrylate | PS80 | 290 | 0.08 | NA | Loperamide | 47 (S) | NA | NA | i.v. | 3.6 | 53.9 (34.2) % MPE | 23 |
| Receptor | PLGA/PVA | Ester | PS80 | 239.9 | 0.187 | 8.2 | Doxorubicin | 75 | NA | NA | i.v. | 3 × 1.5 | 40 % LTS | 27 |
| P188 | 242.4 | 0.211 | 6.0 | i.v. | 40% LTS | |||||||||
| PLGA/HSA | P188 | 408.6 | 0.289 | 8.1 | 97 | 25% LTS | ||||||||
| PLGA/PVA | PS80 | 166.9 | 0.266 | −25.0 | Loperamide | 77 | 7 | 80% MPE | ||||||
| P188 | 168.5 | 0.346 | −17.9 | 80% MPE | ||||||||||
| PLGA/HSA | PS80 | 292.4 | 0.092 | −18.9 | 82 | 40% MPE | ||||||||
| P188 | 287.7 | .077 | −17.5 | 50% MPE | ||||||||||
| Receptor | PLGA/HSA | Ester | P188 | 468 (19) | .404 (.158) | −11.2 | Doxorubicin | 88.5 | Lecithin | 7% | i.v. | 3 × 2.5 | -12.1 (24.1) μg/mm2 | 31 |
| Receptor | Chitosan-PEG | Ether | NA | 637 (2) | NA | 18 (4) | Z-DEVD-FMK | 23 (1) | Transferrin Receptor Mab | NA | i.v. | 1 | PEC | 62 |
| Receptor | PBCA | Acrylate | NA | 300 | 0.177 | NA | Dalargin | (S) | Apo B | 12.5 μg/mL (S) | i.v. | 7.5 | 15.17 (14.11) % MPES | 107 |
| Apo E | 26.08 (21.43) % MPE | |||||||||||||
| PS80 | Apo B | 64.68 (25.61) % MPE | ||||||||||||
| Apo E | 52.09 (11.22) % MPE | |||||||||||||
| NA | Loperamide | (S) | Apo E | 3.6 | 52.8 (35.5) % MPEP | |||||||||
| PS80 | NA | 96.7 (12.1) % MPE | ||||||||||||
| Apo E | 96.7 (12.1) % MPE | |||||||||||||
| Receptor | PEG-PLGA (50:50) | Ester-Ether | NA | 120 | NA | −14 | Urocortin | NA | Lactoferrin | 42/particle | i.v. | 28 μg | 25% | 87 |
| Adsorption | PLGA | Ester | P188 | 155 (26) | 0.13 (0.01) | −15.2 (5.6) | Loperamide | 15.1 (0.7) | g7 peptide | 39 umol/g | i.v. | 2.7 | 60% MPE | 108 |
| Receptor | PEG-PLGA | Ester-Ether | NA | 132 | NA | −21.42 | Novel active | 57.52 | NA | NA | i.v. | 4 | PPT | 29 |
| Adsorption | (25:75) | NA | 151 | −19.59 | peptide | 48.18 | TGN | 25% | 1 | PEC | ||||
| Receptor | PLA | Ester | PVA | 300 or 125TEM | 0.1 or 1.05 | −19.3 (0.5) | Ritonavir | 89.7 | NA | NA | i.v. (d10) | 45 | 10 μg/g | 30 |
| Adsorption | 157TEM | 0.14 or 1.06 | 2.4 (0.3) | TAT | 0.23 μg/mg | 80 μg/g | ||||||||
| Adsorption | P407-Chitosan | Ester-Ether | PEG | 148 (31) | .30 (.01) | 12.1 (0.8) | β-galactosidase | >90 | RVG29 | 1.8% | i.v. | 5 | ∼25% of dose | 63 |
| Cell | NA | NA | P407 | 383 | NA | −10.2 | Atazanavir | 100 (H) | NA | NA | s.c. | 2 × 250 | 10.6 ng/g | 105 |
| 365 | −24.6 | Folate | 40% | 33 ng/g | ||||||||||
| 471 | −21.5 | Ritonavir | NA | 4.1 ng/g | ||||||||||
| 454 | −18.3 | Folate | 40% | 34.5 ng/g | ||||||||||
Values inside parenthesis are composition for core polymer or standard deviation for numerical values.
NA – Not applicable or not analyzed in reference.
Size – Hydrodynamic diameter determined from DLS unless otherwise noted.
Encap % – percentage of drug encapsulated into core polymer. (S) – surface absorption of drug. (H) – core is homogenized drug.
i.v. – intravenous administration via tail vein.
s.c. – subcutaneous administration.
Dosage – mg drug/kg mouse unless otherwise noted. Multiple administrations are listed as number of administrations × dose of drug for each administration.
Response – Various methods utilized to evaluate response compared to either soluble drug or nanoparticle drug without targeting modification: concentration (μg/g, ng/g) given as mass of drug present per mass of brain tissue; PEC – performance equivalent to control; PPT – positive performance to test; MPE – maximal possible effect; LTS – long-term survival; IST – increased survival time.