Multifunctional magnetoliposomes as drug delivery vehicles for the potential treatment of Parkinson’s disease

Autores organización

• Maria Angelica Calderon Pelaez

  Autor

• 

  Myriam Lucia Velandia Romero

  Autor

Autores

• Cifuentes J
• Cifuentes-Almanza S
• Ruiz Puentes P
• Quezada V
• González Barrios AF
• Rafat M
• Muñoz-Camargo C
• Albarracín SL
• Cruz JC

Grupos de investigación

• Grupo de Virología

  

  Investigador

  Jaime Eduardo Castellanos Parra

Resumen

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. Therefore, development of novel technologies and strategies to treat PD is a global health priority. Current treatments include administration of Levodopa, monoamine oxidase inhibitors, catechol-O-methyltransferase inhibitors, and anticholinergic drugs. However, the effective release of these molecules, due to the limited bioavailability, is a major challenge for the treatment of PD. As a strategy to solve this challenge, in this study we developed a novel multifunctional magnetic and redox-stimuli responsive drug delivery system, based on the magnetite nanoparticles functionalized with the high-performance translocating protein OmpA and encapsulated into soy lecithin liposomes. The obtained multifunctional magnetoliposomes (MLPs) were tested in neuroblastoma, glioblastoma, primary human and rat astrocytes, blood brain barrier rat endothelial cells, primary mouse microvascular endothelial cells, and in a PD-induced cellular model. MLPs demonstrated excellent performance in biocompatibility assays, including hemocompatibility (hemolysis percentages below 1%), platelet aggregation, cytocompatibility (cell viability above 80% in all tested cell lines), mitochondrial membrane potential (non-observed alterations) and intracellular ROS production (negligible impact compared to controls). Additionally, the nanovehicles showed acceptable cell internalization (covered area close to 100% at 30 min and 4 h) and endosomal escape abilities (significant decrease in lysosomal colocalization after 4 h of exposure). Moreover, molecular dynamics simulations were employed to better understand the underlying translocating mechanism of the OmpA protein, showing key findings regarding specific interactions with phospholipids. Overall, the versatility and the notable in vitro performance of this novel nanovehicle make it a suitable and promising drug delivery technology for the potential treatment of PD. Copyright © 2023 Cifuentes, Cifuentes-Almanza, Ruiz Puentes, Quezada, González Barrios, Calderón-Peláez, Velandia-Romero, Rafat, Muñoz-Camargo, Albarracín and Cruz.

Copyright © 2023 Cifuentes, Cifuentes-Almanza, Ruiz Puentes, Quezada, González Barrios, Calderón-Peláez, Velandia-Romero, Rafat, Muñoz-Camargo, Albarracín and Cruz.

Keywords

• Biochemistry; Biocompatibility; Blood; Cell culture; Controlled drug delivery; Endothelial cells; Liposomes; Magnetite; Magnetite nanoparticles; Mitochondria; Molecular dynamics; Nanomagnetics; Neurodegenerative diseases; Phospholipids; Rats; Targeted drug delivery; Alzheimer; Drug delivery vehicles; Dynamics simulation; Magnetoliposomes; Molecular dynamic simulation; Nanovehicles; Neurodegenerative disorders; Ompa protein; Parkinson’s disease; Performance; Proteins