Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
J Control Release. 2015 Jan 10;197:97-104. doi: 10.1016/j.jconrel.2014.10.029. Epub 2014 Nov 6.
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.
前列环素 I2（PGI2）及其类似物（如贝前列素钠，BPS）可用于治疗肺动脉高压（PAH）。将 BPS 包封在纳米颗粒中以提供持续释放和靶向能力，将提高 BPS 对 PAH 的治疗效果以及接受该药治疗的患者的生活质量。BPS 被包封在由聚乳酸均聚物和单甲氧基聚乙二醇-聚乳酸嵌段共聚物制成的纳米颗粒中。使用荧光发射罗丹明 S 包封的纳米颗粒检查纳米颗粒在受损肺动脉中的积累。使用野百合碱诱导的 PAH 大鼠模型和缺氧诱导的小鼠模型检查 BPS 包封的纳米颗粒的药理学活性。在各种类型的 BPS 包封的纳米颗粒中，选择了一种纳米颗粒，命名为 BPS-NP，该选择基于体外的持续释放曲线和体内的血液清除曲线。以与 BPS-NP 相似的方式制备荧光发射罗丹明 S 包封的纳米颗粒，并且在野百合碱损伤的肺外周动脉中显示出积累和延长的滞留。每周静脉注射一次 BPS-NP（每次 20μg/kg）可预防野百合碱诱导的肺血管重构和右心室肥大。这种保护程度与单独口服 BPS（每天一次，100μg/kg）相似。每周一次静脉注射 BPS-NP（每次 20μg/kg）也对缺氧诱导的肺血管重构和右心室肥大具有改善作用。BPS-NP 对 PAH 动物模型的有益作用似乎是通过其持续释放和组织靶向特征介导的。由于 BPS 给药剂量和频率降低，BPS-NP 可能对 PAH 患者有用。
