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Development and Characterization of PLGA-Based Multistage Delivery System for Enhanced Payload Delivery to Targeted
Jorge A Palma-Chavez1, Kevin Fuentes2, Brian E Applegate3
1Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843, USA.
Macromolecular Bioscience
|January 4, 2021
Summary
This study developed a novel multistage delivery system (MDS) using poly-lactic-co-glycolic-acid (PLGA) for targeted vascular drug delivery. The PLGA-MDS system enhances nanoparticle margination to inflamed endothelium, improving therapeutic potential.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Vascular Biology
Background:
- Vascular-targeted drug delivery is crucial for treating human diseases.
- Current methods face challenges in efficient delivery to specific vascular sites.
Purpose of the Study:
- To develop and characterize a poly-lactic-co-glycolic-acid (PLGA)-based multistage delivery system (MDS).
- To evaluate the targeting efficiency of functionalized MDS for inflamed endothelium.
Main Methods:
- Fabrication of micron-sized PLGA MDS encapsulating drug-loaded PLGA nanoparticles.
- In vitro release studies and biocompatibility assessment with human endothelial cells.
- Surface functionalization of MDS and nanoparticles with Sialyl-Lewis-A (sLeA) for targeting.
Main Results:
- Successfully encapsulated nanoparticles (76-193 nm) within MDS (3-6 µm).
- Demonstrated sustained nanoparticle release for up to 7 days.
- Functionalized MDS showed a 2.7-fold improvement in endothelial binding under laminar flow.
Conclusions:
- The developed PLGA-MDS is biocompatible and capable of sustained drug release.
- Surface-functionalized MDS effectively targets inflamed endothelium.
- MDS enhances nanoparticle margination to the vascular wall, showing promise as an advanced drug carrier.

