College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA; MRL, Merck & Co, Inc., 126 E. Lincoln Ave, Rahway, NJ 07065, USA.
MRL, Merck & Co, Inc., 126 E. Lincoln Ave, Rahway, NJ 07065, USA.
Int J Pharm. 2019 Sep 10;568:118550. doi: 10.1016/j.ijpharm.2019.118550. Epub 2019 Jul 20.
Implants offer the opportunity to improve patient adherence and real-world outcomes. However, most polymers used today are hydrophobic and limit drug properties suitable for development. Thermoplastic poly(urethanes) (TPUs) form pores upon hydration and may facilitate the development of implants containing drugs exhibiting broadly different properties. We sought to investigate the effect of drug physicochemical properties on permeability through membranes of varying TPU mixture composition; leverage imaging to visualize microstructural changes to the membrane across the TPU mixture composition range; and quantitatively characterize the membrane microstructure using equivalent pore analysis. We observed a correlation between drug hydrophobicity and its permeability through hydrophobic-rich TPU membranes. Conversely, all compounds diffused through hydrophilic-rich TPU membranes at similar rates, regardless of drug properties. Imaging revealed significant microstructure differences between hydrophobic-rich and hydrophilic-rich TPU membranes, supporting hypotheses proposed in our previous study. The hydrated hydrophilic TPU membrane pore area was determined to be 0.583% and its equivalent pore radius was found to be 128 nm, suggesting that hydrophilic TPU membranes may be used to modify the release of small molecular weight drugs and macromolecules. These findings highlight the benefits of hydrophilic TPUs as rate-controlling membranes to modulate the release rate of drugs with varying physicochemical properties.
植入物为改善患者顺应性和实际结果提供了机会。然而，目前使用的大多数聚合物都是疏水性的，限制了适合开发的药物特性。热塑性聚（氨酯）（TPU）在水合时形成孔，并且可能有利于开发含有具有广泛不同性质的药物的植入物。我们试图研究药物物理化学性质对通过不同 TPU 混合物组成的膜的渗透性的影响；利用成像技术可视化膜在 TPU 混合物组成范围内的微观结构变化；并使用等效孔分析定量表征膜的微观结构。我们观察到药物疏水性与其通过富含疏水性 TPU 膜的渗透性之间存在相关性。相反，所有化合物都以相似的速率通过富含亲水性的 TPU 膜扩散，而与药物性质无关。成像揭示了富含疏水性和富含亲水性 TPU 膜之间的显著微观结构差异，支持了我们之前研究中提出的假设。确定水合亲水性 TPU 膜的孔面积为 0.583%，其等效孔径为 128nm，表明亲水性 TPU 膜可用于调节小分子药物和大分子的释放。这些发现强调了亲水性 TPU 作为控释膜的优势，可调节具有不同物理化学性质的药物的释放速率。
