Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats.
To evaluate the effect of coupling of recombinant human serum albumin (rHSA) onto the surface of poly(ethylene glycol)-modified liposome (PEG liposome) on the in vivo disposition characteristics of liposomal doxorubicin (DXR), the pharmacokinetics and tissue distribution of DXR were evaluated after intravenous administration of rHSA-modified PEG (rHSA/PEG) liposomal DXR into tumor-bearing rats. rHSA/PEG liposome prepared using a hetero-bifunctional cross-linker, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP), efficiently encapsulated DXR (over 95%). rHSA/PEG liposomal DXR showed longer blood-circulating property than PEG liposomal DXR and the hepatic and splenic clearances of rHSA/PEG liposomal DXR were significantly smaller than those of PEG liposomal DXR. It was also demonstrated that the disposition of DXR to the heart, one of the organs for DXR-related side-effects, was significantly smaller than free DXR. Furthermore, the tumor accumulation of rHSA/PEG liposomal DXR was significantly larger than that of PEG liposomal DXR. The "therapeutic index", a criterion for therapeutic outcome, for rHSA/PEG liposomal DXR was significantly higher than PEG liposomal DXR. These results clearly indicate that rHSA-conjugation onto the surface of PEG liposome would be a useful approach to increase the effectiveness and safety of PEG liposomal DXR.
Yokoe
Jun-ichi
J
Pharmaceutical Research Division, NIPRO Corporation, Shiga, Japan.
Sakuragi
Shiho
S
Yamamoto
Kayoko
K
Teragaki
Takuya
T
Ogawara
Ken-ichi
K
Higaki
Kazutaka
K
Katayama
Naohisa
N
Kai
Toshiya
T
Sato
Makoto
M
Kimura
Toshikiro
T
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D012709:Serum Albumin / Q000008:administration & dosage*; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D008081:Liposomes; D012709:Serum Albumin; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin