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Prolonging the In Vivo Residence Time of Prostaglandin E1 with Biodegradable Nanoparticles

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Abstract

Purpose

Prostaglandins have potent and diverse biologic activities, but their clinical application is severely restricted, mainly due to rapid inactivation in vivo. In order to modulate the pharmacokinetics of prostaglandin E1 (PGE1), we prepared biodegradable nanoparticles as a drug carrier.

Methods

Nanoparticles encapsulating PGE1 were prepared from a blend of poly(lactic acid) homopolymer and poly(ethylene glycol)-poly(lactide) block copolymer by the solvent diffusion method in the presence of iron.

Results

PGE1 was efficiently and stably embedded in the nanoparticles through interaction with iron, despite being relatively hydrophilic and having unstable chemical properties. Depending on the isomers and molecular weight of poly(lactic acid) selected, PGE1 was gradually released from the nanoparticles at various rates into diluted serum in vitro. Both stable retention of PGE1 in the nanoparticles and coating of the nanoparticles with poly(ethylene glycol) led to an extremely extended blood residence time of PGE1, as well as preferential accumulation in vascular lesions.

Conclusions

These results suggest that the present strategy is useful to advance the clinical application of PGE1 as a therapeutic agent for vascular disorders.

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Acknowledgements

We thank Sachiyo Shibata, Tetsushi Kubota and Yukie Tokura for their assistance with the animal experiments.

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Authors and Affiliations

  1. DDS Institute, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato, Tokyo, 105-8461, Japan

    Tsutomu Ishihara, Miyuki Takahashi, Megumu Higaki & Yutaka Mizushima

  2. Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa, 216-8512, Japan

    Mitsuko Takenaga

  3. Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honcho, Kumamoto, 862-0973, Japan

    Tohru Mizushima

Authors
  1. Tsutomu Ishihara
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  2. Miyuki Takahashi
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  3. Megumu Higaki
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  4. Mitsuko Takenaga
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  5. Tohru Mizushima
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  6. Yutaka Mizushima
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Correspondence to Tsutomu Ishihara.

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Ishihara, T., Takahashi, M., Higaki, M. et al. Prolonging the In Vivo Residence Time of Prostaglandin E1 with Biodegradable Nanoparticles. Pharm Res 25, 1686–1695 (2008). https://doi.org/10.1007/s11095-008-9549-8

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  • DOI: https://doi.org/10.1007/s11095-008-9549-8

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