Development of biodegradable nanoparticles for liver-specific ribavirin delivery

Tsutomu Ishihara, Kohei Kaneko, Tomoaki Ishihara, Tohru Mizushima

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4005-4011
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume103
Issue number12
DOIs
Publication statusPublished - 2013 Mar 18

Fingerprint

Ribavirin
Nanoparticles
Liver
Chronic Hepatitis C
Galectins
Hemolytic Anemia
Hep G2 Cells
Intravenous Administration
Lysine
Antiviral Agents
Cultured Cells
Lactic Acid
Iron
Pharmacokinetics
Phosphates

Keywords

  • Controlled release
  • Encapsulation
  • Hepatocytes
  • Nanoparticles
  • Polymer biodegradation
  • Polymeric drug carrier
  • Site-specific delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Development of biodegradable nanoparticles for liver-specific ribavirin delivery. / Ishihara, Tsutomu; Kaneko, Kohei; Ishihara, Tomoaki; Mizushima, Tohru.

In: Journal of Pharmaceutical Sciences, Vol. 103, No. 12, 18.03.2013, p. 4005-4011.

Research output: Contribution to journalArticle

Ishihara, Tsutomu ; Kaneko, Kohei ; Ishihara, Tomoaki ; Mizushima, Tohru. / Development of biodegradable nanoparticles for liver-specific ribavirin delivery. In: Journal of Pharmaceutical Sciences. 2013 ; Vol. 103, No. 12. pp. 4005-4011.
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