Table II.
Mechanism-Based Approaches Used to Determine Kpuu, Brain Values After Administration of the Drug Alone, as well as After Administration of the Drug in the Presence of Liposomes, as well as After Administration of the Drug Loaded in the Liposomal Formulation
| Liposomal formulation | Drug | Kpuu, brain values | Drug delivery enhancement | Formulation | Administration dosage | Refs | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Free drug | Coadministration free drug + liposomes | Drug-loaded liposome | Free drug + liposome-free drug | Free drug/drug-loaded liposome | |||||||||
| Kpuu, free drug | Kpuu, free drug + liposome | Kpuu, drug in liposome | Kpuu, free + lipo control/Kpuu, drug free | Kpuu, drug in lipo/Kpuu, free | EYPC | HSPC | Cholesterol | PEG | Loading dose | Constant infusion | |||
| GSH-PEG liposomal (EYPC phospholipid) | DAMGO | 0.09 | NA | 0.2 | NA | 2.3 | 1000 mM | N/A | 750 mM | 18 mM mPEG2000-DSPE (1 mol%) | 75 μg/min/kg free DAMGO; 1250 μg liposomal DAMGO/min/kg for 10 min | 60 μg/min/kg of free DAMGO and liposomal DAMGO for 2 h | (121) |
| GSH-PEG liposomal (EYPC phospholipid) | DAMGO | 0.05 | 0.05 | 0.1 | 1.0 | 2.0 | 100 mM | N/A | 750 mM | 18 mM mPEG2000-DSPE (1 mol%) | 75 μg/min/kg free DAMGO, liposome emulsion (1250 μg DAMGO/min/kg) for 10 min | 60 μg/min/kg of free DAMGO and liposomal DAMGO for 2 h | (123) |
| PEG liposomal (EYPC phospholipid) | DAMGO | 0.05 | 0.05 | 0.08 | 1.0 | 1.6 | |||||||
| PEG liposomal (EYPC phospholipid) | DPH | 3.00 | 2.3 | 1.50 | 0.8 | 0.5 | 100 mM | N/A | 66 mM | 8.7 mM mPEG2000-DSPE (5 mol%) | 4.5 mg/kg (150 μg/min/kg) of PEG liposomal and 4.5 mg/kg free DPH for 30 min (short infusion regiment) | (122) | |
| PEG liposomal (EYPC phospholipid) – low dose of liposome | MTX | 0.10 | NA | 0.28 | NA | 2.8 | 100 mM | N/A | 66 mM | 8.7 mM mPEG2000-DSPE (5 mol%) | 2.3 mg/kg (77 mg/min/kg) and free MTX of 7.2 μg/min/kg for 30 min | 2.3 mg/kg (77 mg/min/kg) and free MTX of 6 μg/min/kg for 9.5 h | (53) |
| PEG liposomal (EYPC phospholipid) –high dose of liposome | MTX | 0.10 | NA | 0.32 | NA | 3.2 | 15 mg/kg (500 mg/min/kg) and free MTX of 7.2 μg/min/kg for 30 min | 15 mg/kg (500 mg/min/kg) and free MTX of 6 μg/min/kg for 9.5 h | |||||
| PEG liposomal (HSPC phospholipid) | MTX | 0.10 | NA | 0.11 | 98 | 1.1 | N/A | 100 mM | 15 mg/kg (500 mg/min/kg) and free MTX of 7.2 μg/min/kg for 30 min | 15 mg/kg (500 mg/min/kg) and free MTX of 6 μg/min/kg for 9.5 h | |||
| PEG liposomal (EYPC phospholipid) | MTX | 0.10 | 0.09 | 1.50 | 0.9 | 15.0 | 100 mM | N/A | 66 mM | 1.7 mM mPEG2000-DSPE (1 mol%) | Free MTX of 7.2 μg/min/kg and liposomal formulation 15 mg/kg for 30 min | Liposomal formulation of 15 mg/kg and free MTX of 6 μg/min/kg for 9.5 h | (49) |
| GSH-PEG liposomal (EYPC phospholipid) | MTX | 0.10 | 0.09 | 0.53 | 0.9 | 5.3 | |||||||
| PEG liposomal (HSPC phospholipid) | MTX | 0.10 | 0.09 | 0.23 | 0.9 | 2.3 | N/A | 100 mM | |||||
| GSH-PEG liposomal (HSPC phospholipid) | MTX | 0.10 | 0.09 | 0.82 | 0.9 | 8.2 | |||||||
DAMGO [D-Ala2, N-MePhe4, Gly-ol]-enkephalin, DHP diphenhydramine, MTX methotrexate