Tai Yulei, Tian Menglun, Chen Yu, You Peijun, Song Xiaojun, Xu Bangting, Duan Cidong, Jin Dazhi
School Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, China.
Front Chem. 2023 Sep 14;11:1249293. doi: 10.3389/fchem.2023.1249293. eCollection 2023.
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.
氯硝柳胺（NIC）是一种多功能药物，可调节多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，其低水溶性限制了其疗效。在本研究中，将具有良好生物相容性、生物降解性和非免疫原性的聚乳酸-羟基乙酸共聚物（PLGA）和透明质酸（HA）与氯硝柳胺偶联，采用微流控技术制备了PLGA-HA-氯硝柳胺聚合物纳米颗粒（NIC@PLGA-HA）。所获得的微球具有均匀的尺寸分布，平均粒径为442.0±18.8 nm，zeta电位为-25.4±0.41 mV，表明它们在水中稳定分散。载药效率为8.70%。载药微球在pH 7.4和5.0时表现出缓释行为，但在pH 2.0时没有，药物释放动力学由准一级动力学方程描述。采用MTT法检测载药微球对Caco-2细胞增殖的影响。通过微流控技术制备的亲水性HA修饰的NIC@PLGA-HA微球增加了Caco-2细胞的摄取。与相同浓度的NIC相比，由于PLGA、HA和NIC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。因此，利用微流技术合成的pH响应性NIC@PLGA-HA微球提高了NIC的溶解度并改善了其生物活性，从而满足了对肠道药物载体的需求。
