Preparation of PLGA microspheres loaded with niclosamide via microfluidic technology and their inhibition of Caco-2 cell activity in vitro

Frontiers in Chemistry

Chemistry

Bangting Xu¹  Xiaojun Song²  Dazhi Jin²  Menglun Tian²  Cidong Duan²  Yu Chen²  Peijun You²  Yulei Tai² 

[1] School Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China;School Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China;Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, China;

关键词: niclosamide;    poly(lactic-co-glycolic acid);    hyaluronic acid;    microfluidic technology;    cell activity;   

DOI  :  10.3389/fchem.2023.1249293

 received in 2023-06-28, accepted in 2023-09-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Tai, Tian, Chen, You, Song, Xu, Duan and Jin.