Development and pharmacokinetics of galactosylated poly-L-glutamic acid as a biodegradable carrier for liver-specific drug delivery.
OBJECTIVE
A biodegradable carrier for the liver-specific delivery of drugs was developed using poly-L-glutamic acid (PLGA) modified with galactose (galactosylated PLGA or Gal-PLGA), and its feasibility was investigated in mice.


METHODS
111In-PLGA and 111In-Gal-PLGAs were injected in mice and their distribution and biodegradation properties were studied.


RESULTS
After intravenous injection. 111In-PLGA was rapidly eliminated from the plasma and recovered mainly in the kidneys and urine. Approximately 15% of the dose was recovered in the liver, predominantly in the nonparenchymal cells. 111In-Gal-PLGAs were taken up by the liver parenchymal cells. Derivatives having 16 or more galactose residues were taken up by the liver to a higher extent (> 60% of the dose). The hepatic clearance of 111In-Gal-PLGAs correlated with their number of galactose residues. 111In-Gal18-PLGA was degraded into low-molecular weight products in the liver.


CONCLUSIONS
The advantageous in vivo properties of Gal-PLGA as a liver-specific biodegradable carrier of drugs were demonstrated in mice.
Hirabayashi
H
H
Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Nishikawa
M
M
Takakura
Y
Y
Hashida
M
M
D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004337:Drug Carriers; D016503:Drug Delivery Systems; D007205:Indium Radioisotopes; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D004337:Drug Carriers; D007205:Indium Radioisotopes; D011099:Polyglutamic Acid