Inhaled PLGA particles of prostaglandin E₁ ameliorate symptoms and progression of pulmonary hypertension at a reduced dosing frequency.
Inhaled PLGA particles of prostaglandin E₁ ameliorate symptoms and progression of pulmonary hypertension at a reduced dosing frequency.
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DOI：
10.1021/mp300426u
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发表时间：
2013-05-06
影响因子：
4.9
通讯作者：
Ahsan F
中科院分区：
文献类型：
--
作者：
Gupta V;Gupta N;Shaik IH;Mehvar R;Nozik-Grayck E;McMurtry IF;Oka M;Komatsu M;Ahsan F
本研究旨在研究前列腺素E1（PGE1）（一种强效肺血管扩张剂）的非侵入性和长效聚合物颗粒制剂在缓解肺动脉高压（PH）体征和逆转病变肺中发生的生化变化方面的疗效。PH大鼠，单次皮下注射野百合碱（MCT）开发的，用两种类型的PGE1，多孔和无孔的聚合物颗粒，intraperheal或静脉内平原PGE1。对于慢性研究，大鼠接受了每日一次或三次的肠内多孔聚（乳酸-羟基乙酸共聚物）（PLGA）颗粒，或每日三次的普通PGE1，连续10天，通过肠内或静脉内给药。通过测量平均肺动脉压（MPAP）、评价右心室肥大和评估各种分子和细胞标记物（包括肌化程度、血小板聚集、基质金属蛋白酶-2（MMP-2）和增殖细胞核抗原（PCNA））来研究制剂对疾病进展的影响。在接受10天治疗的大鼠中，普通PGE 1和大多孔颗粒PGE 1都降低了MPAP和右心室肥大（RVH）。与普通PGE1相比，PGE1的聚合物多孔颗粒在降低的给药频率下产生相同的效果，并且对全身血液动力学造成最小的脱靶效应。显微镜和免疫组化研究表明，多孔颗粒的PGE1也降低了程度的肌肉化，血管性血友病因子（vWF）和PCNA表达的PH大鼠肺。总的来说，我们的研究表明，与普通PGE1相比，PGE1负载的可吸入颗粒制剂改善PH症状并以降低的给药频率阻止疾病进展。
This study sought to investigate the efficacy of a noninvasive and long acting polymeric particle based formulation of prostaglandin E1 (PGE1), a potent pulmonary vasodilator, in alleviating the signs of pulmonary hypertension (PH) and reversing the biochemical changes that occur in the diseased lungs. PH rats, developed by a single subcutaneous injection of monocrotaline (MCT), were treated with two types of polymeric particles of PGE1, porous and nonporous, and intratracheal or intravenous plain PGE1. For chronic studies, rats received either intratracheal porous poly (lactic-co-glycolic acid) (PLGA) particles, once- or thrice-a-day, or plain PGE1 thrice-a-day for 10 days administered intratracheally or intravenously. The influence of formulations on disease progression was studied by measuring the mean pulmonary arterial pressure (MPAP), evaluating right ventricular hypertrophy and assessing various molecular and cellular makers including the degree of muscularization, platelet aggregation, matrix metalloproteinase-2 (MMP-2) and proliferating cell nuclear antigen (PCNA). Both plain PGE1 and large porous particles of PGE1 reduced MPAP and right ventricular hypertrophy (RVH) in rats that received the treatments for 10 days. Polymeric porous particles of PGE1 produced the same effects at a reduced dosing frequency compared to plain PGE1 and caused minimal off-target effects on systemic hemodynamics. Microscopic and immunohistochemical studies revealed that porous particles of PGE1 also reduced the degree of muscularization, von Willebrand factor (vWF) and PCNA expression in the lungs of PH rats. Overall, our study suggests that PGE1 loaded inhalable particulate formulations improve PH symptoms and arrest the progression of disease at a reduced dosing frequency compared to plain PGE1.
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DOI：
10.1152/ajplung.00258.2006
发表时间：
2007-04-01
影响因子：
4.9
作者：
Crossno, Joseph T.;Garat, Chrystelle V.;Klemm, Dwight J.
通讯作者：
Klemm, Dwight J.
影响因子：
56.9
作者：
Edwards, DA;Hanes, J;Langer, R
通讯作者：
Langer, R
DOI：
10.1164/ajrccm/137.1.5
发表时间：
1988-01-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
COX, JW;ANDREADIS, NA;VASSAR, MJ
通讯作者：
VASSAR, MJ
影响因子：
24.3
作者：
Ghofrani, HA;Friese, G;Lohmeyer, J
通讯作者：
Lohmeyer, J
影响因子：
3.8
作者：
Harush-Frenkel, Oshrat;Bivas-Benita, Maytal;Benita, Simon
通讯作者：
Benita, Simon