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Development and Pharmacokinetics of Galactosylated Poly-L-Glutamic Acid as a Biodegradable Carrier for Liver-Specific Drug Delivery

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Abstract

Purpose. 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 111n-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.

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Hirabayashi, H., Nishikawa, M., Takakura, Y. et al. Development and Pharmacokinetics of Galactosylated Poly-L-Glutamic Acid as a Biodegradable Carrier for Liver-Specific Drug Delivery. Pharm Res 13, 880–884 (1996). https://doi.org/10.1023/A:1016053128569

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  • DOI: https://doi.org/10.1023/A:1016053128569

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