Pre-coating with serum albumin reduces receptor-mediated hepatic disposition of polystyrene nanosphere: implications for rational design of nanoparticles.
We evaluated the in vivo disposition characteristics of polystyrene nanospheres (NS) with the particle size of 50 nm (NS-50) pre-coated with human serum albumin (HSA) after intravenous administration in rats. HSA-coated NS-50 showed much longer blood-circulating property and the hepatic uptake clearance for HSA-coated NS-50 was about 1/5 of that for NS-50. In parallel with the results obtained in the in vivo study, liver perfusion experiments also showed that the hepatic disposition of HSA-coated NS-50 was much less than that of NS-50 in the presence of serum in the perfusate. To unravel the mechanism behind the less affinity of HSA-coated NS-50 to the liver, serum proteins associated on the surface was quantitatively and qualitatively assessed. The results indicated that pre-coated HSA impaired subsequent association of serum proteins onto the surface, suggesting that the association of a given serum protein with opsonic activity might be suppressed by HSA pre-coating. From these findings, pre-coating of nanoparticles with serum albumin could be useful to prevent their rapid clearance by mononuclear phagocyte system in vivo.
Ogawara
Ken-ichi
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Furumoto
Kentaro
K
Nagayama
Susumu
S
Minato
Keiko
K
Higaki
Kazutaka
K
Kai
Toshiya
T
Kimura
Toshikiro
T
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010477:Perfusion; D011137:Polystyrenes / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000276:immunology; D012709:Serum Albumin / Q000276:immunology*; D014357:Trypsin / Q000737:chemistry
D001798:Blood Proteins; D011137:Polystyrenes; D011994:Recombinant Proteins; D012709:Serum Albumin; D014357:Trypsin