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Development of biodegradable nanoparticles for liver-specific ribavirin delivery.

Abstract
Ribavirin is an antiviral drug used for the treatment of chronic hepatitis C. However, ribavirin induces severe side effects such as hemolytic anemia. In this study, we prepared biodegradable nanoparticles as ribavirin carriers to modulate the pharmacokinetics of the drug. The nanoparticles encapsulating ribavirin monophosphate (RMP) were prepared from the blend of poly(d,l-lactic acid) homopolymer and arabinogalactan (AG)-poly(l-lysine) conjugate by using the solvent diffusion method in the presence of iron (III). RMP was efficiently and stably embedded in the nanoparticles and gradually released for 37 days in phosphate-buffered saline at 37°C. The coating of AG on the nanoparticles surfaces was verified by measuring the zeta potentials and performing an aggregation test of the nanoparticles using galactose-binding lectin. Moreover, the nanoparticles were efficiently internalized in cultured HepG2 cells. Ribavirin was drastically accumulated to the liver of mice after intravenous administration of the RMP-loaded nanoparticles, after which the ribavirin content gradually decreased for at least 7 days. Our results indicated successful development of nanoparticles with dual functions, targeting to the liver and sustained release of ribavirin, and suggested that the present strategy could help to advance the clinical application of ribavirin as a therapeutic agent for chronic hepatitis C.
AuthorsTsutomu Ishihara, Kohei Kaneko, Tomoaki Ishihara, Tohru Mizushima
JournalJournal of pharmaceutical sciences (J Pharm Sci) Vol. 103 Issue 12 Pg. 4005-4011 (Dec 2014) ISSN: 1520-6017 [Electronic] United States
PMID25335768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Chemical References
  • Antiviral Agents
  • Biocompatible Materials
  • Delayed-Action Preparations
  • Excipients
  • Galactans
  • Polyesters
  • Polymers
  • Polylysine
  • Lactic Acid
  • poly(lactide)
  • Ribavirin
  • arabinogalactan
Topics
  • Animals
  • Antiviral Agents (administration & dosage, chemistry)
  • Biocompatible Materials (administration & dosage, chemistry)
  • Cell Line, Tumor
  • Delayed-Action Preparations (administration & dosage, chemistry)
  • Drug Delivery Systems (methods)
  • Excipients (administration & dosage, chemistry)
  • Female
  • Galactans (administration & dosage, chemistry)
  • Hep G2 Cells
  • Hepatitis C, Chronic (drug therapy)
  • Humans
  • Lactic Acid (administration & dosage, chemistry)
  • Liver (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles (administration & dosage, chemistry)
  • Polyesters
  • Polylysine (administration & dosage, chemistry)
  • Polymers (administration & dosage, chemistry)
  • Ribavirin (administration & dosage, chemistry)

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