Dual Coating of Chitosan and Albumin Negates the Protein Corona-Induced Reduced Vascular Adhesion of Targeted PLGA Microparticles in Human Blood

Abstract

Vascular-targeted carriers (VTCs) have the potential to localize therapeutics and imaging agents to inflamed, diseased sites. Poly (lactic-co-glycolic acid) (PLGA) is a negatively charged copolymer commonly used to construct VTCs due to its biodegradability and FDA approval. Unfortunately, PLGA VTCs experienced reduced adhesion to inflamed endothelium in the presence of human plasma proteins. In this study, PLGA microparticles were coated with chitosan (CS), human serum albumin (HSA), or both (HSA-CS) to improve adhesion. The binding of sialyl Lewis A (a ligand for E-selectin)-targeted PLGA, HSA-PLGA, CSPLGA, and HSA-CSPLGA to activated endothelial cells was evaluated in red blood cells in buffer or plasma flow conditions. PLGA VTCs with HSA-only coating showed improvement and experienced 35–52% adhesion in plasma compared to plasma-free buffer conditions across all shear rates. PLGA VTCs with dual coating—CS and HSA—maintained 80% of their adhesion after exposure to plasma at low and intermediate shears and ≈50% at high shear. Notably, the protein corona characterization showed increases at the 75 and 150 kDa band intensities for HSA-PLGA and HSA-CSPLGA, which could correlate to histidine-rich glycoprotein and immunoglobulin G. The changes in protein corona on HSA-coated particles seem to positively influence particle binding, emphasizing the importance of understanding plasma protein–particle interactions.

Interaction of Serum and Plasma Proteins with Polyelectrolyte Microparticles with Core/Shell and Shell-Only Structures

“…Microplastic particles coated with model proteins before incubation in protein-containing media behave differently in protein–cell interactions . Precoating with human serum albumin (HSA) reduced the negative effect of plasma protein adsorption on the adhesion of poly­(lactic- co -glycolic acid) microparticles to the endothelium …”

“… 24 Precoating with human serum albumin (HSA) reduced the negative effect of plasma protein adsorption on the adhesion of poly(lactic- co -glycolic acid) microparticles to the endothelium. 25 …”

Interaction of Human Serum and Plasma Proteins with Polyelectrolyte Microcapsules of Different Structures

“…Precoating with human serum albumin (HSA) allows reducing the negative effect of plasma protein adsorption on the adhesion of poly(lactic-co-glycolic acid) microparticles to the endothelium 25 .…”