biostudies-literaturePalma-Chavez JAAmerican Heart AssociationAmerican Heart Association-American Stroke AssociationNational Cancer InstituteNCI NIH HHSQatar National Research FundCancer Prevention and Research Institute of TexasNational Science Foundatione2000377https://www.ebi.ac.uk/biostudies/studies/S-EPMC8203499biostudies-literatureUnknown21(3)Vascular-targeted drug delivery remains an attractive platform for therapeutic and diagnostic interventions in human diseases. This work focuses on the development of a poly-lactic-co-glycolic-acid (PLGA)-based multistage delivery system (MDS). MDS consists of two stages: a micron-sized PLGA outer shell and encapsulated drug-loaded PLGA nanoparticles. Nanoparticles with average diameters of 76, 119, and 193 nm are successfully encapsulated into 3-6 µm MDS. Sustained in vitro release of nanoparticles from MDS is observed for up to 7 days. Both MDS and nanoparticles arebiocompatible with human endothelial cells. Sialyl-Lewis-A (sLe^A ) is successfully immobilized on the MDS and nanoparticle surfaces to enable specific targeting of inflamed endothelium. Functionalized MDS demonstratMacromolecular bioscienceDevelopment and Characterization of PLGA-Based Multistage Delivery System for Enhanced Payload Delivery to Targeted Vascular Endothelium.PMC8203499NPRP8‐1606‐3‐32217SDG33660894RP1805881R01CA218739R01 CA218739HRD – 1810995Palma-Chavez JAApplegate BEJo JAFuentes KCharoenphol PfalseDevelopment and Characterization of PLGA-Based Multistage Delivery System for Enhanced Payload Delivery to Targeted Vascular Endothelium.Vascular-targeted drug delivery remains an attractive platform for therapeutic and diagnostic interventions in human diseases. This work focuses on the development of a poly-lactic-co-glycolic-acid (PLGA)-based multistage delivery system (MDS). MDS consists of two stages: a micron-sized PLGA outer shell and encapsulated drug-loaded PLGA nanoparticles. Nanoparticles with average diameters of 76, 119, and 193 nm are successfully encapsulated into 3-6 µm MDS. Sustained in vitro release of nanoparticles from MDS is observed for up to 7 days. Both MDS and nanoparticles arebiocompatible with human endothelial cells. Sialyl-Lewis-A (sLe^A ) is successfully immobilized on the MDS and nanoparticle surfaces to enable specific targeting of inflamed endothelium. Functionalized MDS demonstrat2021-01-01T00:00:00Z2021 Mar2025-04-04T10:16:18.016Z2025-04-04T10:16:18.016ZS-EPMC82034993339321710.1002/mabi.202000377