硫酸葡聚糖凝胶包衣用于药物洗脱球囊血管成形术

Jenna A. Mosier, Hannah M. Stealey, Kalifa Stringfield, Katie Webb, L. Simpson
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摘要

血管钙化是心血管疾病的一个后果,它会扰乱血液的自然流动,并可能导致死亡。常用的治疗手段包括各种消炎药、球囊血管成形术或支架,但在完全逆转钙化方面收效甚微。提出的设计重点是通过开发一种以葡聚糖磺酸盐为基础的凝胶给药系统来改善现有的药物洗脱支架,该系统装载核κ b配体受体激活剂(RANKL)来诱导破骨细胞分化。为了确保凝胶能够正确地传递RANKL,我们测试了凝胶对羟基磷灰石(HA)的亲和力,HA是钙化的关键成分,并且测试了凝胶的抗剪切能力。红外光谱(IR)显示与HA结合。初步扫描电镜和能量色散x射线能谱(SEM/EDS)结果证实,在HA混合物中浸泡一小时后,凝胶上存在钙。剪切测试表明,在流动条件下,可忽略不计的蛋白质被剪切,平均为0.029±0.024 μg/mL,表明凝胶在球囊输送期间是稳定的。这些初步结果表明,以葡聚糖磺酸盐为基础的凝胶有潜力作为治疗血管钙化的凝胶涂层。未来的实验将包括一项共培养研究,以确定破骨细胞祖细胞是否会在负载rankl的凝胶存在下正常增殖和分化。关键词:血管成形术;钙化;心血管疾病;右旋糖酐;凝胶;破骨细胞;支架;血管
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Dextran Sulfate Based Gel Coating for Drug Eluting Balloon Angioplasty
Vascular calcification, a consequence of cardiovascular disease, disrupts natural blood flow and can result in death. Common treatment efforts include various anti-inflammatory medications, balloon angioplasty, or stents, with little success in completely reversing calcification. The proposed design focuses on improving current drug-eluting stents by developing a dextran-sulfate-based gel drug delivery system loaded with receptor activator of nuclear kappa B-ligand (RANKL) to induce osteoclast differentiation. To ensure that the gel could properly deliver RANKL, the gel was tested for its affinity for hydroxyapatite (HA), a critical component of calcification, and its ability to withstand shear. Infrared spectroscopy (IR) indicated binding to HA. Preliminary scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM/EDS) results confirmed the presence of calcium on the gel after a one-hour soak in a HA mixture. Shear testing demonstrated that negligible protein, an average of 0.029± 0.024 μg/mL, was sheared off under flow conditions, indicating that the gel is stable for duration of balloon delivery. These preliminary results indicate that a dextran-sulfate-based gel has potential to serve as a therapeutic gel-coating to treat vascular calcification. Future experimentation will include a co-culture study to determine whether osteoclast progenitor cells will properly proliferate and differentiate in the presence of the RANKL-loaded gel. KEYWORDS: Angioplasty; Calcification; Cardiovascular; Dextran; Gel; Osteoclast; Stent; Vascular
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