Mejía Susana P, López Daniela, Cano Luz Elena, Naranjo Tonny W, Orozco Jahir
Max Planck Tandem Group in Nanobioengineering, Institute of Chemistry, Faculty of Natural and Exact Sciences, University of Antioquia, Complejo Ruta N, Calle 67 N° 52-20, Medellin 050010, Colombia.
Experimental and Medical Micology Group, Corporación para Investigaciones Biológicas (CIB), UdeA, UPB, UdeS, Medellin 050010, Colombia.
Pharmaceutics. 2022 Sep 13;14(9):1932. doi: 10.3390/pharmaceutics14091932.
Infectious diseases caused by intracellular microorganisms such as represent a significant challenge worldwide. Drug encapsulation into functionalized nanoparticles (NPs) is a valuable alternative to improving drug solubility and bioavailability, preventing undesirable interactions and drug degradation, and reaching the specific therapeutic target with lower doses. This work reports on Itraconazole (ITZ) encapsulated into core-shell-like polymeric NPs and functionalized with anti-F4/80 antibodies for their targeted and controlled release into macrophages. Uptake assay on co-culture showed significant differences between the uptake of functionalized and bare NPs, higher with functionalized NPs. In vitro assays showed that F4/80-NPs with 0.007 µg/mL of encapsulated ITZ eliminated the fungus in co-culture with macrophages effectively compared to the bare NPs, without any cytotoxic effect on macrophages after 24 h interaction. Furthermore, encapsulated ITZ modulated the gene expression of anti and pro-inflammatory cytokines (IL-1, INF-Y, IL-6 and IL-10) on macrophages. Additionally, the anti-F4/80 antibody-coating enhanced natural and adequate antifungal response in the cells, exerting a synergistic effect that prevented the growth of the fungus at the intracellular level. Functionalized NPs can potentially improve macrophage-targeted therapy, increasing NPs endocytosis and intracellular drug concentration.
由细胞内微生物引起的传染病，如……在全球范围内构成重大挑战。将药物封装到功能化纳米颗粒（NPs）中是提高药物溶解度和生物利用度、防止不良相互作用和药物降解以及以较低剂量达到特定治疗靶点的一种有价值的替代方法。这项工作报道了将伊曲康唑（ITZ）封装到核壳状聚合物纳米颗粒中，并用抗F4/80抗体进行功能化，以实现其向巨噬细胞的靶向和控释。共培养的摄取试验表明，功能化纳米颗粒和裸纳米颗粒的摄取存在显著差异，功能化纳米颗粒的摄取更高。体外试验表明，与裸纳米颗粒相比，包封有0.007 µg/mL ITZ的F4/80纳米颗粒在与巨噬细胞共培养时能有效消除真菌，在24小时相互作用后对巨噬细胞没有任何细胞毒性作用。此外，包封的ITZ调节了巨噬细胞上抗炎和促炎细胞因子（IL-1、INF-Y、IL-6和IL-10）的基因表达。此外，抗F4/80抗体涂层增强了细胞内天然且充分的抗真菌反应，发挥了协同作用，在细胞内水平上阻止了真菌生长。功能化纳米颗粒有可能改善巨噬细胞靶向治疗，增加纳米颗粒的内吞作用和细胞内药物浓度。
