Blakney Anna K, Simonovsky Felix I, Suydam Ian T, Ratner Buddy D, Woodrow Kim A
Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, United States.
Department of Chemistry, Seattle University, 901 12th Ave., Seattle, Washington 98122, United States.
ACS Biomater Sci Eng. 2016 Sep 12;2(9):1595-1607. doi: 10.1021/acsbiomaterials.6b00346. Epub 2016 Jul 13.
Sustained release of physicochemically diverse drugs from electrospun fibers remains a challenge and precludes the use of fibers in many medical applications. Here, we synthesize a new class of polyurethanes with poly(lactic-co-glycolic acid) (PLGA) moieties that degrade faster than polyurethanes based on polycaprolactone. The new polymers, with varying hard to soft segment ratios and fluorobenzene pendant group content, were electrospun into nanofibers and loaded with four physicochemically diverse small molecule drugs. Polymers were characterized using GPC, XPS, and F NMR. The size and morphology of electrospun fibers were visualized using SEM, and drug/polymer compatibility and drug crystallinity were evaluated using DSC. We measured drug release, polymer degradation and cell-culture cytotoxicity of biodegradation products. We show that these newly synthesized PLGA-based polyurethanes degrade up to 65-80% within 4 weeks and are cytocompatible . The drug-loaded electrospun fibers were amorphous solid dispersions. We found that increasing the hard to soft segment ratio of the polymer enhances the sustained release of positively charged drugs, whereas increasing the fluorobenzene pendant content caused more rapid release of some drugs. In summary, increasing the hard segment or fluorobenzene pendant content of segmented polyurethanes containing PLGA moieties allows for modulation of physicochemically diverse drug release from electrospun fibers while maintaining a biologically relevant biodegradation rate.
从电纺纤维中持续释放物理化学性质各异的药物仍然是一个挑战，这也阻碍了纤维在许多医学应用中的使用。在此，我们合成了一类新型的带有聚（乳酸-乙醇酸）（PLGA）基团的聚氨酯，其降解速度比基于聚己内酯的聚氨酯更快。将具有不同硬段与软段比例以及氟苯侧基含量的新型聚合物电纺制成纳米纤维，并负载四种物理化学性质各异的小分子药物。使用凝胶渗透色谱法（GPC）、X射线光电子能谱法（XPS）和氟核磁共振法（F NMR）对聚合物进行表征。使用扫描电子显微镜（SEM）观察电纺纤维的尺寸和形态，并使用差示扫描量热法（DSC）评估药物/聚合物相容性以及药物结晶度。我们测量了药物释放情况、聚合物降解情况以及生物降解产物的细胞培养细胞毒性。我们发现这些新合成 的基于PLGA 的聚氨酯在4周内降解高达
65 - 80%，并且具有细胞相容性。负载药物的电纺纤维是无定形固体分散体。我们发现，增加聚合物的硬段与软段比例可增强带正电荷药物的持续释放，而增加氟苯侧基含量则会使某些药物释放更快
。总之，增加含有PLGA 基团的嵌段聚氨酯的硬段或氟苯侧基含量，可以在维持生物学相关降解速率的同时，调节从电纺纤维中释放物理化学性质各异的药物。
