Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb® Pro: Formulation aspects and nanoparticle stability to nebulization
Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb® Pro: Formulation aspects and nanoparticle stability to nebulization
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DOI：
10.1016/j.ijpharm.2011.10.012
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发表时间：
2012-01-17
影响因子：
5.8
通讯作者：
Schmehl, Thomas
中科院分区：
文献类型：
--
作者：
Beck-Broichsitter, Moritz;Kleimann, Pia;Schmehl, Thomas
聚合物纳米颗粒满足了对药物递送应用的日益增长的兴趣，并且在改善药物向肺部的受控递送方面具有很大的希望。在这里，我们提出了一系列研究，进行这些研究是为了了解制剂变量对新型可生物降解的装载西地那非的纳米颗粒的雾化性能的影响，所述纳米颗粒设计用于威胁生命的肺动脉高压的靶向气雾剂治疗。以聚乙烯醇（PVA）为稳定剂，采用溶剂蒸发法制备了D，L-丙交酯-乙交酯共聚物纳米粒子（粒径约为200 nm）。使用Aeroneb（R）Pro雾化器的空气动力学和输出特性与用于雾化的所用流体的动态粘度良好相关。雾化性能主要受所采用的稳定剂的量的影响，而不是由所施加的纳米颗粒浓度。纳米颗粒显示出对雾化过程中产生的力的物理稳定性，这归因于纳米颗粒周围吸附的PVA层。将西地那非成功包封到纳米粒中（包封率：类似于80%）。纳米粒的大小、粒径分布和西地那非含量不受雾化的影响，体外药物释放曲线显示西地那非的持续释放超过120 min。目前的研究表明，制备的西地那非纳米粒是一种有前途的治疗肺动脉高压的药物。(c)2011 Elsevier B. V.保留所有权利。
Polymeric nanoparticles meet the increasing interest for drug delivery applications and hold great promise to improve controlled drug delivery to the lung. Here, we present a series of investigations that were carried out to understand the impact of formulation variables on the nebulization performance of novel biodegradable sildenafil-loaded nanoparticles designed for targeted aerosol therapy of life-threatening pulmonary arterial hypertension.Narrowly distributed poly(D, L-lactide-co-glycolide) nanoparticles (size: similar to 200 nm) were prepared by a solvent evaporation technique using poly(vinyl alcohol) (PVA) as stabilizer. The aerodynamic and output characteristics using the Aeroneb (R) Pro nebulizer correlated well with the dynamic viscosity of the employed fluids for nebulization. The nebulization performance was mainly affected by the amount of employed stabilizer, rather than by the applied nanoparticle concentration. Nanoparticles revealed physical stability against forces generated during aerosolization, what is attributed to the adsorbed PVA layer around the nanoparticles. Sildenafil was successfully encapsulated into nanoparticles (encapsulation efficiency: similar to 80%). Size, size distribution and sildenafil content of nanoparticles were not affected by nebulization and the in vitro drug release profile demonstrated a sustained sildenafil release over similar to 120 min.The current study suggests that the prepared sildenafil-loaded nanoparticles are a promising pharmaceutical for the therapy of pulmonary arterial hypertension. (c) 2011 Elsevier B.V. All rights reserved.