Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure

Abstract

The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier–wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid–polyaspartamide copolymer. The latter was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC–drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.

Novel dual-flow perfusion bioreactor for in vitro pre-screening of nanoparticles delivery: design, characterization and testing

“…Polymeric fluorescent nanoparticles (FNPs) based on a fluorescent polyaspartamide-polylactide graft copolymer were synthesized [38,39] and use as drug carrier model. The transport, adhesion and distribution on blood flow of similar particles were previously evaluated to elucidate the FNPs transport toward the vessel vasculature in micro-capillary flow [40]. Here, FNPs were utilized to understand the contribution of the bioreactor perfusion flow to the mobility and distribution of particles inside polymeric scaffolds.…”

Biomedical Applications of Polylactide (PLA) and Its Copolymers

“…Craparo et al reported a study on a PLA-based nanoparticulate carrier margination in relation to RBC concentration (hematocrit) and pressure drop by using a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro [ 2 ], highlighting the importance of taking into account RBC–drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.…”