Influence of PEI as a core modifying agent on PLGA microspheres of PGE₁, a pulmonary selective vasodilator.
Influence of PEI as a core modifying agent on PLGA microspheres of PGE₁, a pulmonary selective vasodilator.
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PEI作为核心修饰剂对PGE₁的PLGA微球的影响，PGE₁是肺选择性血管扩张剂。
DOI：
10.1016/j.ijpharm.2011.04.017
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发表时间：
2011-07-15
影响因子：
5.8
通讯作者：
Ahsan, Fakhrul
中科院分区：
文献类型：
--
作者：
Gupta, Vivek;Ahsan, Fakhrul
关键词：
本研究验证了一种假设，即聚乙烯亚胺(PEI)修饰的大孔聚(乳酸-乙醇酸)(PLGA)微粒是前列腺素E1(PGE1)肺部给药的有效载体，用于治疗肺血管疾病--肺动脉高压(PAH)。以PEI-25 kDa为内水相，采用复乳化溶剂挥发法制备了具有渗透压梯度的微球。用聚乙烯醇(PVA)包覆纳米粒子。对颗粒的形态、大小、空气动力学直径、比表面积、孔体积和体外释放情况进行了检测。对具有最佳吸入性能的微粒进行了体内肺吸收、大鼠肺匀浆代谢稳定性以及大鼠支气管肺泡灌洗液和呼吸道上皮细胞CALU-3急性毒性的测试。微粒学数据表明，PEI修饰的PGE1微粒最适合吸入。加入PEI后，1%PVA和2%PVA的包封率分别为83.26±3.04%和95.48±0.46%。模拟肺间质液的累积释药量在50.8±0.76%~55.36±0.06%之间。当通过肺部给药时，观察到循环半衰期显著延长，最高可达6.0-6.5小时。代谢稳定性和毒性研究表明，优化的处方在生理条件下是稳定的，对肺和呼吸道上皮相对安全。总体而言，这项研究表明，大孔可吸入聚合物微粒是治疗PAH的非侵入性和可控性释放PGE1的可行选择。
This study tests the hypothesis that large porous poly (lactic-co-glycolic acid) (PLGA) microparticles modified with polyethyleneimine (PEI) are viable carriers for pulmonary delivery of prostaglandin E1 (PGE1) used in the treatment of pulmonary arterial hypertension (PAH), a pulmonary vascular disorder. The particles were prepared by a double-emulsion solvent evaporation method with PEI-25 kDa in the internal aqueous phase to produce an osmotic pressure gradient. Polyvinyl alcohol (PVA) was used for external coating of the particles. The particles were examined for morphology, size, aerodynamic diameter, surface area, pore volume and in-vitro release profiles. Particles with optimal properties for inhalation were tested for in-vivo pulmonary absorption, metabolic stability in rat lung homogenates, and acute toxicity in rat bronchoalveolar lavage fluid and respiratory epithelial cells, Calu-3. The micromeritic data indicated that the PEI-modified particles of PGE1 are optimal for inhalation. Incorporation of PEI in the formulations resulted in an increased entrapment efficiency–83.26±3.04% for particles with 1% PVA and 95.48±0.46% for particles with 2% PVA. The amount of cumulative drug released into the simulated interstitial lung fluid was between 50.8±0.76% and 55.36±0.06%. A remarkable extension of the circulation half-life up to 6.0–6.5 hours was observed when the formulations were administered via the lungs. The metabolic stability and toxicity studies showed that the optimized formulations were stable at physiological conditions and relatively safe to the lungs and respiratory epithelium. Overall, this study demonstrates that large porous inhalable polymeric microparticles can be a feasible option for non-invasive and controlled release of PGE1 for treatment of PAH.
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影响因子：
5.8
作者：
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通讯作者：
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