Encapsulation of beraprost sodium in nanoparticles: Analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension

Tomoaki Ishihara, Erika Hayashi, Shuhei Yamamoto, Chisa Kobayashi, Yuichi Tamura, Ryoichi Sawazaki, Fumiya Tamura, Kayoko Tahara, Tadashi Kasahara, Tsutomu Ishihara, Mitsuko Takenaga, Keiichi Fukuda, Tohru Mizushima

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Prostaglandin I2 (PGI2) and its analogues (such as beraprost sodium, BPS) are beneficial for the treatment of pulmonary arterial hypertension (PAH). The encapsulation of BPS in nanoparticles to provide sustained release and targeting abilities would improve both the therapeutic effect of BPS on PAH and the quality of life of patients treated with this drug. BPS was encapsulated into nanoparticles prepared from a poly(lactic acid) homopolymer and monomethoxy poly(ethyleneglycol)-poly(lactide) block copolymer. The accumulation of nanoparticles in damaged pulmonary arteries was examined using fluorescence-emitting rhodamine S-encapsulated nanoparticles. The monocrotaline-induced PAH rat model and the hypoxia-induced mouse model were used to examine the pharmacological activity of BPS-encapsulated nanoparticles. A nanoparticle, named BPS-NP, was selected among various types of BPS-encapsulated nanoparticles tested; this was based on the sustained release profile in vitro and blood clearance profile in vivo. Fluorescence-emitting rhodamine S-encapsulated nanoparticles were prepared in a similar manner to that of BPS-NP, and showed accumulation and prolonged residence in monocrotaline-damaged pulmonary peripheral arteries. Intravenous administration of BPS-NP (once per week, 20 μg/kg) protected against monocrotaline-induced pulmonary arterial remodeling and right ventricular hypertrophy. The extent of this protection was similar to that observed with oral administration (once per day, 100 μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20 μg/kg) also exhibited an ameliorative effect on hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy. The beneficial effects of BPS-NP on PAH animal models seem to be mediated by its sustained release and tissue targeting profiles. BPS-NP may be useful for the treatment of PAH patients due to reduced dosages and frequency of BPS administration.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalJournal of Controlled Release
Volume197
DOIs
Publication statusPublished - 2015 Jan 10

Fingerprint

beraprost
Pulmonary Hypertension
Nanoparticles
Animal Models
Pharmacology
Monocrotaline
Right Ventricular Hypertrophy
Rhodamines
Intravenous Administration
Pulmonary Artery

Keywords

  • Beraprost sodium
  • Biodegradable nanoparticle
  • Encapsulation
  • Prostaglandin I
  • Pulmonary arterial hypertension

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Encapsulation of beraprost sodium in nanoparticles : Analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension. / Ishihara, Tomoaki; Hayashi, Erika; Yamamoto, Shuhei; Kobayashi, Chisa; Tamura, Yuichi; Sawazaki, Ryoichi; Tamura, Fumiya; Tahara, Kayoko; Kasahara, Tadashi; Ishihara, Tsutomu; Takenaga, Mitsuko; Fukuda, Keiichi; Mizushima, Tohru.

In: Journal of Controlled Release, Vol. 197, 10.01.2015, p. 97-104.

Research output: Contribution to journalArticle

Ishihara, Tomoaki ; Hayashi, Erika ; Yamamoto, Shuhei ; Kobayashi, Chisa ; Tamura, Yuichi ; Sawazaki, Ryoichi ; Tamura, Fumiya ; Tahara, Kayoko ; Kasahara, Tadashi ; Ishihara, Tsutomu ; Takenaga, Mitsuko ; Fukuda, Keiichi ; Mizushima, Tohru. / Encapsulation of beraprost sodium in nanoparticles : Analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension. In: Journal of Controlled Release. 2015 ; Vol. 197. pp. 97-104.
@article{560b8cdbdf114ac1b9bf97d1466fbbb2,
title = "Encapsulation of beraprost sodium in nanoparticles: Analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension",
abstract = "Prostaglandin I2 (PGI2) and its analogues (such as beraprost sodium, BPS) are beneficial for the treatment of pulmonary arterial hypertension (PAH). The encapsulation of BPS in nanoparticles to provide sustained release and targeting abilities would improve both the therapeutic effect of BPS on PAH and the quality of life of patients treated with this drug. BPS was encapsulated into nanoparticles prepared from a poly(lactic acid) homopolymer and monomethoxy poly(ethyleneglycol)-poly(lactide) block copolymer. The accumulation of nanoparticles in damaged pulmonary arteries was examined using fluorescence-emitting rhodamine S-encapsulated nanoparticles. The monocrotaline-induced PAH rat model and the hypoxia-induced mouse model were used to examine the pharmacological activity of BPS-encapsulated nanoparticles. A nanoparticle, named BPS-NP, was selected among various types of BPS-encapsulated nanoparticles tested; this was based on the sustained release profile in vitro and blood clearance profile in vivo. Fluorescence-emitting rhodamine S-encapsulated nanoparticles were prepared in a similar manner to that of BPS-NP, and showed accumulation and prolonged residence in monocrotaline-damaged pulmonary peripheral arteries. Intravenous administration of BPS-NP (once per week, 20 μg/kg) protected against monocrotaline-induced pulmonary arterial remodeling and right ventricular hypertrophy. The extent of this protection was similar to that observed with oral administration (once per day, 100 μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20 μg/kg) also exhibited an ameliorative effect on hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy. The beneficial effects of BPS-NP on PAH animal models seem to be mediated by its sustained release and tissue targeting profiles. BPS-NP may be useful for the treatment of PAH patients due to reduced dosages and frequency of BPS administration.",
keywords = "Beraprost sodium, Biodegradable nanoparticle, Encapsulation, Prostaglandin I, Pulmonary arterial hypertension",
author = "Tomoaki Ishihara and Erika Hayashi and Shuhei Yamamoto and Chisa Kobayashi and Yuichi Tamura and Ryoichi Sawazaki and Fumiya Tamura and Kayoko Tahara and Tadashi Kasahara and Tsutomu Ishihara and Mitsuko Takenaga and Keiichi Fukuda and Tohru Mizushima",
year = "2015",
month = "1",
day = "10",
doi = "10.1016/j.jconrel.2014.10.029",
language = "English",
volume = "197",
pages = "97--104",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

TY - JOUR

T1 - Encapsulation of beraprost sodium in nanoparticles

T2 - Analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension

AU - Ishihara, Tomoaki

AU - Hayashi, Erika

AU - Yamamoto, Shuhei

AU - Kobayashi, Chisa

AU - Tamura, Yuichi

AU - Sawazaki, Ryoichi

AU - Tamura, Fumiya

AU - Tahara, Kayoko

AU - Kasahara, Tadashi

AU - Ishihara, Tsutomu

AU - Takenaga, Mitsuko

AU - Fukuda, Keiichi

AU - Mizushima, Tohru

PY - 2015/1/10

Y1 - 2015/1/10

N2 - Prostaglandin I2 (PGI2) and its analogues (such as beraprost sodium, BPS) are beneficial for the treatment of pulmonary arterial hypertension (PAH). The encapsulation of BPS in nanoparticles to provide sustained release and targeting abilities would improve both the therapeutic effect of BPS on PAH and the quality of life of patients treated with this drug. BPS was encapsulated into nanoparticles prepared from a poly(lactic acid) homopolymer and monomethoxy poly(ethyleneglycol)-poly(lactide) block copolymer. The accumulation of nanoparticles in damaged pulmonary arteries was examined using fluorescence-emitting rhodamine S-encapsulated nanoparticles. The monocrotaline-induced PAH rat model and the hypoxia-induced mouse model were used to examine the pharmacological activity of BPS-encapsulated nanoparticles. A nanoparticle, named BPS-NP, was selected among various types of BPS-encapsulated nanoparticles tested; this was based on the sustained release profile in vitro and blood clearance profile in vivo. Fluorescence-emitting rhodamine S-encapsulated nanoparticles were prepared in a similar manner to that of BPS-NP, and showed accumulation and prolonged residence in monocrotaline-damaged pulmonary peripheral arteries. Intravenous administration of BPS-NP (once per week, 20 μg/kg) protected against monocrotaline-induced pulmonary arterial remodeling and right ventricular hypertrophy. The extent of this protection was similar to that observed with oral administration (once per day, 100 μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20 μg/kg) also exhibited an ameliorative effect on hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy. The beneficial effects of BPS-NP on PAH animal models seem to be mediated by its sustained release and tissue targeting profiles. BPS-NP may be useful for the treatment of PAH patients due to reduced dosages and frequency of BPS administration.

AB - Prostaglandin I2 (PGI2) and its analogues (such as beraprost sodium, BPS) are beneficial for the treatment of pulmonary arterial hypertension (PAH). The encapsulation of BPS in nanoparticles to provide sustained release and targeting abilities would improve both the therapeutic effect of BPS on PAH and the quality of life of patients treated with this drug. BPS was encapsulated into nanoparticles prepared from a poly(lactic acid) homopolymer and monomethoxy poly(ethyleneglycol)-poly(lactide) block copolymer. The accumulation of nanoparticles in damaged pulmonary arteries was examined using fluorescence-emitting rhodamine S-encapsulated nanoparticles. The monocrotaline-induced PAH rat model and the hypoxia-induced mouse model were used to examine the pharmacological activity of BPS-encapsulated nanoparticles. A nanoparticle, named BPS-NP, was selected among various types of BPS-encapsulated nanoparticles tested; this was based on the sustained release profile in vitro and blood clearance profile in vivo. Fluorescence-emitting rhodamine S-encapsulated nanoparticles were prepared in a similar manner to that of BPS-NP, and showed accumulation and prolonged residence in monocrotaline-damaged pulmonary peripheral arteries. Intravenous administration of BPS-NP (once per week, 20 μg/kg) protected against monocrotaline-induced pulmonary arterial remodeling and right ventricular hypertrophy. The extent of this protection was similar to that observed with oral administration (once per day, 100 μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20 μg/kg) also exhibited an ameliorative effect on hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy. The beneficial effects of BPS-NP on PAH animal models seem to be mediated by its sustained release and tissue targeting profiles. BPS-NP may be useful for the treatment of PAH patients due to reduced dosages and frequency of BPS administration.

KW - Beraprost sodium

KW - Biodegradable nanoparticle

KW - Encapsulation

KW - Prostaglandin I

KW - Pulmonary arterial hypertension

UR - http://www.scopus.com/inward/record.url?scp=84911443774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911443774&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2014.10.029

DO - 10.1016/j.jconrel.2014.10.029

M3 - Article

C2 - 25449809

AN - SCOPUS:84911443774

VL - 197

SP - 97

EP - 104

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -