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Abstract：
Niclosamide (NIC) is a multifunctional drug that regulates various signaling pathways and biological processes. It is widely used for the treatment of cancer, viral infections, and metabolic disorders. However, its low water solubility limits its efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) and hyaluronic acid (HA), which exhibit good biocompatibility, biodegradability, and non-immunogenicity, were conjugated with niclosamide to prepare PLGA-HA-niclosamide polymeric nanoparticles (NIC@PLGA-HA) using microfluidic technology. The obtained microspheres had a uniform size distribution, with an average mean size of 442.0 ± 18.8 nm and zeta potential of -25.4 ± 0.41 mV, indicating their stable dispersion in water. The drug-loading efficiency was 8.70%. The drug-loaded microspheres showed sustained release behavior at pH 7.4 and 5.0, but not at pH 2.0, and the drug release kinetics were described by a quasi-first-order kinetic equation. The effect of the drug-loaded microspheres on the proliferation of Caco-2 cells was detected using the MTT assay. Hydrophilic HA-modified NIC@PLGA-HA microspheres prepared via microfluidic technology increased the cellular uptake by Caco-2 cells. Compared to the same concentration of NIC, the NIC@PLGA-HA microspheres demonstrated a stronger inhibitory effect on Caco-2 cells owing to the combined effect of PLGA, HA, and NIC. Therefore, the pH-responsive NIC@PLGA-HA microspheres synthesized using microfluid technology increased the solubility of NIC and improved its biological activity, thus contributing to the demand for intestinal drug carriers.
摘要：
氯硝柳胺（NIC）是一种多功能药物，可调节各种信号通路和生物过程。它被广泛用于治疗癌症，病毒感染,和代谢紊乱。然而,它的低水溶性限制了它的功效。在这项研究中,聚（乳酸-乙醇酸）（PLGA）和透明质酸（HA），表现出良好的生物相容性，生物降解性，和非免疫原性，采用微流控技术与氯硝柳胺偶联制备PLGA-HA-氯硝柳胺聚合物纳米颗粒(NIC@PLGA-HA)。获得的微球具有均匀的尺寸分布，平均尺寸为442.0±18.8nm，zeta电位为-25.4±0.41mV，表明它们在水中的稳定分散。载药效率为8.70%。载药微球在pH7.4和5.0时表现出持续释放行为，但在pH2.0时则没有，药物释放动力学由准一级动力学方程描述。用MTT法检测载药微球对Caco-2细胞增殖的影响。通过微流体技术制备的亲水性HA修饰的NIC@PLGA-HA微球增加了Caco-2细胞的细胞摄取。与相同浓度的NIC相比，由于PLGA的联合作用，NIC@PLGA-HA微球对Caco-2细胞表现出更强的抑制作用，HA,和NIC。因此,微流体技术合成的pH响应型NIC@PLGA-HA微球增加了NIC的溶解度,提高了其生物活性,从而促进了对肠道药物载体的需求。
