Effect of TRX-liposomes size on their prolonged circulation in rats.
Newly formulated cationic liposomes (TRX-liposomes) with four different mean diameters were injected into twelve male rats via the lateral tail vein in order to evaluate the effect of liposomal size on pharmacokinetic parameters. TRX-liposomes disappeared from the blood according to the one-compartment model and demonstrated maximum and minimum half-lives of ca. 14 h (mean diameter of 114.3 nm) and ca. 5 h (mean diameter of 285.9 nm), respectively. This prolonged half-life tended to decrease at the boundary of 114.3 nm mean diameter. The optimal size (114.3 nm) for prolonged circulation of TRX-liposomes was consistent with that of pegylated liposomes such as Doxil((R)), however, the half-life was different among these liposomes. The electric charge of the TRX-liposomal surface is assumed to be responsible for this difference. The results of the present study will be very useful in the design of long-circulating cationic liposomes.
Kawahara
Kazuo
K
R&D Center, Terumo Corporation, Kanagawa, Japan.
Sekiguchi
Arinobu
A
Kiyoki
Emiko
E
Ueda
Tsutomu
T
Shimamura
Kyoko
K
Kurosaki
Yasuo
Y
Miyaoka
Shozo
S
Okabe
Hiromitsu
H
Miyajima
Masaharu
M
Kimura
Junji
J
D000818:Animals; D001550:Benzamidines / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology; D005227:Fatty Acids / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D008081:Liposomes; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
C450860:3,5-dipentadecyloxybenzamidine hydrochloride; D001550:Benzamidines; D005227:Fatty Acids; D008081:Liposomes