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
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Health, Labour, and Welfare of Japan ( 201307008A and 201208005B ), as well as Center of Innovation Program from Japan Science and Technology Agency , Scientific Technique Research Promotion Program for Agriculture, Forestry and Food Industry (26048A) , and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan ( 22117515 ).
Publisher Copyright:
Copyright © 2014 Elsevier B.V. All rights reserved.
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, 20μg/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, 100μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20μg/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, 20μg/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, 100μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20μg/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(2)
KW - Pulmonary arterial hypertension
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U2 - 10.1016/j.jconrel.2014.10.029
DO - 10.1016/j.jconrel.2014.10.029
M3 - Article
C2 - 25449809
AN - SCOPUS:84911443774
SN - 0168-3659
VL - 197
SP - 97
EP - 104
JO - Journal of controlled release : official journal of the Controlled Release Society
JF - Journal of controlled release : official journal of the Controlled Release Society
ER -