Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy.
The results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycol-derivatized phospholipid have a pronounced effect on liposome tissue distribution and can produce a large increase in the pharmacological efficacy of encapsulated antitumor drugs. This effect is substantially greater than that observed previously with conventional liposomes and is associated with a more than 5-fold prolongation of liposome circulation time in blood, a marked decrease in uptake by tissues such as liver and spleen, and a corresponding increased accumulation in implanted tumors. These and other properties described here have expanded considerably the prospects of liposomes as an effective carrier system for a variety of pharmacologically active macromolecules.
Papahadjopoulos
D
D
Department of Pharmacology, University of California, San Francisco 94143.
Allen
T M
TM
Gabizon
A
A
Mayhew
E
E
Matthay
K
K
Huang
S K
SK
Lee
K D
KD
Woodle
M C
MC
Lasic
D D
DD
Redemann
C
C
D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D004355:Drug Stability; D015251:Epirubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D008081:Liposomes / Q000493:pharmacokinetics; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D014018:Tissue Distribution
D004337:Drug Carriers; D005710:Gallium Radioisotopes; D008081:Liposomes; D015251:Epirubicin; D004317:Doxorubicin