Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application.

Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application.
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DOI:
10.3390/jfb14020052
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发表时间:
2023-01-17
影响因子:
4.8
通讯作者:
--
中科院分区:
工程技术3区
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--
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椎间盘(IVD)损伤可导致慢性疼痛和残疾,目前的治疗方法都无法完全恢复其功能。一些非手术治疗方法已显示出一定的前景;然而,这些方法通常受到多种分子的突释和定位不良的限制。在这项概念验证研究中,我们开发了一种纳米颗粒(NP)递送系统,以高效递送高溶解度和低溶解度的药物分子。通过水包油乳液制备了与1 - 氧代 - 1H - 吡啶并[2,1 - b][1,3]苯并噁唑 - 3 - 羧酸(PBC,一种新型荧光染料)共轭的醋酸纤维素和聚己内酯 - 聚乙二醇纳米颗粒。使用了两种药物,水不溶性的吲哚美辛(IND)和水溶性的4 - 氨基吡啶(4 - AP)来研究它们的释放模式。电子显微镜证实了纳米颗粒的球形性质和粗糙表面。粒度分析显示,基于动态光散射,流体动力学半径约为150 - 162 nm。Zeta电位随着PBC共轭而增加,表明其稳定性增强。IND的包封效率几乎是4 - AP的3倍,释放可持续长达4天,这表明溶解度提高,而4 - AP的释放可持续长达7天。纳米颗粒及其药物制剂没有显示出任何明显的细胞毒性,并且可被人椎间盘髓核细胞摄取。当在体内注射到小鼠尾椎椎间盘时,纳米颗粒保留在髓核细胞内以及椎间盘的髓核和纤维环的注射部位。这些荧光纳米制剂可作为一种平台技术,将治疗药物递送到椎间盘以及其他需要局部药物注射的组织。
Damage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In this proof-of-concept study, we developed a nanoparticle (NP) delivery system to efficiently deliver high- and low-solubility drug molecules. Nanoparticles of cellulose acetate and polycaprolactone-polyethylene glycol conjugated with 1-oxo-1H-pyrido [2,1-b][1,3]benzoxazole-3-carboxylic acid (PBC), a novel fluorescent dye, were prepared by the oil-in-water emulsion. Two drugs, a water insoluble indomethacin (IND) and a water soluble 4-aminopyridine (4-AP), were used to study their release patterns. Electron microscopy confirmed the spherical nature and rough surface of nanoparticles. The particle size analysis revealed a hydrodynamic radius ranging ~150–162 nm based on dynamic light scattering. Zeta potential increased with PBC conjugation implying their enhanced stability. IND encapsulation efficiency was almost 3-fold higher than 4-AP, with release lasting up to 4 days, signifying enhanced solubility, while the release of 4-AP continued for up to 7 days. Nanoparticles and their drug formulations did not show any apparent cytotoxicity and were taken up by human IVD nucleus pulposus cells. When injected into coccygeal mouse IVDs in vivo, the nanoparticles remained within the nucleus pulposus cells and the injection site of the nucleus pulposus and annulus fibrosus of the IVD. These fluorescent nano-formulations may serve as a platform technology to deliver therapeutic agents to IVDs and other tissues that require localized drug injections.
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