Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time.
Transfer of MPEG(1900)-DSPE from micellar phase to pre-formed liposomes imparts long in vivo circulation half-life to an otherwise rapidly cleared lipid composition. MPEG(1900)-DSPE transfers efficiently and quickly in a time and temperature dependent manner. There is negligible content leakage and a strong correlation between assayed mol% MPEG(1900)-DSPE, liposome diameter increase, and pharmacokinetic parameters such as distribution phase half-life. Since a biological attribute (liposome clearance rate) can be modified by the insertion process, it suggests a simple and economical way to impart site-specific targeting to a variety of liposome delivery systems. This method is also a convenient way to measure the 'brush' thickness of such conjugates directly.
Uster
P S
PS
SEQUUS Pharmaceuticals, Inc., Menlo Park, CA 94025, USA. paulu@sequus.com
Allen
T M
TM
Daniel
B E
BE
Mendez
C J
CJ
Newman
M S
MS
Zhu
G Z
GZ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D010714:Phosphatidylethanolamines / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D008081:Liposomes; C099730:N-carbamylmethoxypoly(ethylene glycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols