Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Biomater Sci. 2020 May 21;8(10):2797-2813. doi: 10.1039/c9bm01775e. Epub 2020 Feb 21.
Benign prostatic hyperplasia (BPH) is a prevalent urological disease affecting elders. Currently, the prostatic artery embolization (PAE) is considered as a minimally invasive and safe technique to treat BPH. However, various drug-loaded embolic agents have not been thoroughly investigated in BPH therapy. In this study, finasteride/poly(3-hydroxybutyrate-3-hydroxyvalerate)@polyvinyl alcohol/chitosan (FNS/PHBV@PVA/CS) reservoir-type microspheres were prepared via the solid-in-water-in-oil (S/W/O) emulsion crosslinking method with the aim to reduce the burst effect and control localized drug delivery. The structure and properties of the drug and resultant microspheres were characterized via field emission scanning electron microscopy (FESEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the drug-loaded hybrid microspheres were well-dispersed and spherical with a mean diameter of 238.1 ± 27.3 μm. All samples exhibited excellent thermal stability. The FNS/PHBV microspheres were successfully encapsulated inside the PVA/CS polymeric matrix, which effectively suppressed the burst effect and prolonged the drug release up to 51 days. In vitro biocompatibility assessment indicated that the microspheres possessed excellent cytocompatibility and hemocompatibility. Furthermore, in vivo studies performed in the rabbit ear embolization model showed the formation of progressive ischemic necrosis after treatment for various periods. Histopathological studies revealed that the microspheres completely occluded the blood vessels with minimal foreign body response and formed the fibrotic area at the periphery of embolized arteries. Furthermore, the auricular vascular endothelial cells showed acute ultrastructural changes, associated with the ischemic necrosis induced by the embolization procedures. All these findings suggest that the FNS/PHBV@PVA/CS hybrid microspheres could be used as a promising drug delivery system for potential applications in BPH therapy.
良性前列腺增生（BPH）是一种常见的影响老年人的泌尿科疾病。目前，前列腺动脉栓塞术（PAE）被认为是治疗 BPH 的一种微创且安全的技术。然而，在 BPH 治疗中，尚未对各种载药栓塞剂进行彻底研究。在这项研究中，通过固-水-油（S/W/O）乳液交联法制备了非那雄胺/聚（3-羟基丁酸-3-羟基戊酸酯）@聚乙烯醇/壳聚糖（FNS/PHBV@PVA/CS）储库型微球，旨在减少突释效应并控制局部药物释放。通过场发射扫描电子显微镜（FESEM）、傅里叶变换红外（FTIR）光谱、X 射线衍射（XRD）和热重分析（TGA）对药物和所得微球的结构和性能进行了表征。结果表明，载药混合微球分散均匀，呈球形，平均直径为 238.1±27.3μm。所有样品均表现出优异的热稳定性。FNS/PHBV 微球成功地被包裹在 PVA/CS 聚合物基质中，有效地抑制了突释效应，并将药物释放延长至 51 天。体外生物相容性评估表明，微球具有优异的细胞相容性和血液相容性。此外，在兔耳栓塞模型中的体内研究表明，在不同时间段的治疗后，可形成进行性缺血性坏死。组织病理学研究表明，微球完全闭塞血管，仅有最小的异物反应，并在栓塞动脉的周围形成纤维性区域。此外，耳血管内皮细胞显示出急性超微结构变化，这与栓塞过程引起的缺血性坏死有关。所有这些发现表明，FNS/PHBV@PVA/CS 杂化微球可用作有前途的药物递送系统，可潜在应用于 BPH 治疗。
