Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages
Infectious diseases caused by intracellular microorganisms such as <i>Histoplasma capsulatum</i> represent a significant challenge worldwide. Drug encapsulation into functionalized nanoparticles (NPs) is a valuable alternative to improving drug solubility and bioavailability, preventing...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/9/1932 |
| _version_ | 1797483615360122880 |
|---|---|
| author | Susana P. Mejía Daniela López Luz Elena Cano Tonny W. Naranjo Jahir Orozco |
| author_facet | Susana P. Mejía Daniela López Luz Elena Cano Tonny W. Naranjo Jahir Orozco |
| author_sort | Susana P. Mejía |
| collection | DOAJ |
| description | Infectious diseases caused by intracellular microorganisms such as <i>Histoplasma capsulatum</i> 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 <i>H. capsulatum</i> 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. |
| first_indexed | 2024-03-09T22:49:33Z |
| format | Article |
| id | doaj.art-96c682eb03694954a297426a78429964 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:49:33Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-96c682eb03694954a297426a784299642023-11-23T18:23:19ZengMDPI AGPharmaceutics1999-49232022-09-01149193210.3390/pharmaceutics14091932Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for MacrophagesSusana P. Mejía0Daniela López1Luz Elena Cano2Tonny W. Naranjo3Jahir Orozco4Max 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, ColombiaExperimental and Medical Micology Group, Corporación para Investigaciones Biológicas (CIB), UdeA, UPB, UdeS, Medellin 050010, ColombiaExperimental and Medical Micology Group, Corporación para Investigaciones Biológicas (CIB), UdeA, UPB, UdeS, Medellin 050010, ColombiaExperimental and Medical Micology Group, Corporación para Investigaciones Biológicas (CIB), UdeA, UPB, UdeS, Medellin 050010, ColombiaMax 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, ColombiaInfectious diseases caused by intracellular microorganisms such as <i>Histoplasma capsulatum</i> 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 <i>H. capsulatum</i> 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.https://www.mdpi.com/1999-4923/14/9/1932<i>Histoplasma capsulatum</i>PLGAItraconazolemacrophagefunctionalized nanoparticleF4/80 receptor |
| spellingShingle | Susana P. Mejía Daniela López Luz Elena Cano Tonny W. Naranjo Jahir Orozco Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages Pharmaceutics <i>Histoplasma capsulatum</i> PLGA Itraconazole macrophage functionalized nanoparticle F4/80 receptor |
| title | Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages |
| title_full | Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages |
| title_fullStr | Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages |
| title_full_unstemmed | Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages |
| title_short | Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages |
| title_sort | antifungal encapsulated into ligand functionalized nanoparticles with high specificity for macrophages |
| topic | <i>Histoplasma capsulatum</i> PLGA Itraconazole macrophage functionalized nanoparticle F4/80 receptor |
| url | https://www.mdpi.com/1999-4923/14/9/1932 |
| work_keys_str_mv | AT susanapmejia antifungalencapsulatedintoligandfunctionalizednanoparticleswithhighspecificityformacrophages AT danielalopez antifungalencapsulatedintoligandfunctionalizednanoparticleswithhighspecificityformacrophages AT luzelenacano antifungalencapsulatedintoligandfunctionalizednanoparticleswithhighspecificityformacrophages AT tonnywnaranjo antifungalencapsulatedintoligandfunctionalizednanoparticleswithhighspecificityformacrophages AT jahirorozco antifungalencapsulatedintoligandfunctionalizednanoparticleswithhighspecificityformacrophages |