MECHANICALLY RESPONSIVE MICROAGGREGATES FOR SITE-SPECIFIC DRUG DELIVERY

Mazen M. El-Hammadi – Post-Doc, Universidad de Sevilla; María Dolores Cayero-Otero – Assistant Professor, Universidad de Sevilla; Lucía Martín-Navarro – PhD Student, Universidad de Sevilla; Maripaz Jiménez-Guerrero – Researcher, Universidad de Sevilla; Noelia Sola-Idígora – Researcher, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain; David Fernández Rivas – Associate Professor, Mesoscale Chemical Systems Group, Department of Chemical Engineering (DCE), Faculty of Science and Technology, University of Twente, The Netherlands; Elena Castro-Hernández – Associate Professor, Ingeniería Aeroespacial y Mecánica de Fluidos, Universidad de Sevilla; Josefa Álvarez-Fuentes – Assistant Professor, Universidad de Sevilla; Remedios Otero-Candelera – Clinician-Scientist, Respiratory Department, Virgen del Rocio Universitary Hospital, Sevilla, Spain; Lucía Martín-Banderas – Associate Professor, Universidad de Sevilla

Introduction:

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism (PE), is a major cause of death and long-term disability worldwide. Fibrinolytic therapy is required in high-risk or refractory patients but is limited by bleeding due to non-selective drug distribution. Vascular beds with pathological obstruction or physiologically narrow geometries generate elevated shear stress that can be harnessed for targeted delivery¹. We present shear-sensitive PLGA microaggregates that disassemble under high shear, enabling preferential nanoparticle delivery to target vessels.

Learning Objectives:

• -Evaluate the shear-responsive disassembly of PLGA microaggregates in microfluidic and cellular models.
• -Analyze nanoparticle cell uptake following microaggregate collapse under elevated shear stress.
• -Assess the in vivo biodistribution of PLGA microaggregates and their targeting capacity.