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.
Highlights
Nanomedicine holds great promises in the treatment of a wide range of diseases, such as cancer, pain, infections and inflammatory disorders [1,2]
The term refers to the flow behavior of white blood cells (WBCs) and platelets, which concentrate in the red blood cells (RBCs)-free-layer (RBC-FL), a near-wall region depleted of RBCs, which originates from the migration of RBCs toward the vessel centerline due to a hydrodynamic lift [5,6,7]
This aim was reached by using polymeric fluorescent nanoparticles (FNPs) with nanometric size, highly hydrophilic surface and low zeta potential, that were prepared by following a well-known method such as the high pressure homogenization (HPH) [15]
Summary
Nanomedicine holds great promises in the treatment of a wide range of diseases, such as cancer, pain, infections and inflammatory disorders [1,2]. Molecules 2017, 22, 1845 target with minimal toxicity and in a controlled manner For this purpose, the use of nano- and micro-particulate drug delivery systems has emerged as a valuable potential tool for performing the main goals of nanomedicine (e.g., targeted delivery, stability of the drug, high permeability, controlled release-kinetic and reduced side-effects) [2]. To evaluate the potential in delivery efficiency of drug carriers, it is crucial to study their transport, adhesion and distribution in blood flow. The phenomenon of margination has been studied either by numerical simulations [8,11] or by experimental studies in vitro, the latter being focused on the dependence of micro-particles (μ-Ps) distribution and delivery efficacy on the presence of RBCs, shear rate, particle size, shape and surface charge [3,9,12,13]. Margination is affected by μ-P size and shape, larger spherical/discoid particles being more effectively marginated both in vitro and in vivo [14]
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