pH-driven enhancement of anti-tubercular drug loading on iron oxide nanoparticles for drug delivery in macrophages

[摘要] Nanoparticle deployment in drug delivery is contingent upon controlled drug loading and a desired release profile, with simultaneous biocompatibility and cellular targeting. Iron oxide nanoparticles (IONPs), being biocompatible, are used as drug carriers.However, to prevent aggregation of bare IONPs, they are coated with stabilizing agents. We hypothesize that, zwitterionic drugslike norfloxacin (NOR, a fluoroquinolone) can manifest dual functionality – nanoparticle stabilization and antibiotic activity, eliminating the need of a separate stabilizing agent. Since these drugs have different charges, depending on the surrounding pH, drugloading enhancement could be pH dependent. Hence, upon synthesizing IONPs, they were coated with NOR, either at pH 5 (predominantly as cationic, NOR+) or at pH 10 (predominantly as anionic, NOR−). We observed that, drug loading at pH 5 exceededthat at pH 10 by 4.7–5.7 times. Furthermore, only the former (pH 5 system) exhibited a desirable slower drug release profile, compared to the free drug. NOR-coated IONPs also enable a 22 times higher drug accumulation in macrophages, compared to identicalextracellular concentrations of the free drug. Thus, lowering the drug coating pH to 5 imparts multiple benefits – improved IONPstability, enhanced drug coating, higher drug uptake in macrophages at reduced toxicity and slower drug release.

[学科分类] 环境监测和分析

[关键词] drug-nanoparticle interactions;drug uptake;intra-macrophage;ironoxide nanoparticles;norfloxacin