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Molecules 2017, 22(11), 1845; doi:10.3390/molecules22111845

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

1
Laboratory of Biocompatible Polymers, Dipartimento di Scienze e Tecnologie, Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo-via Archirafi, 32-90123 Palermo, Italy
2
Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, P.le V. Tecchio 80, 80125 Napoli, Italy
3
IBF-CNR, 90143 Palermo, Italy
4
Mediterranean Center for Human Health Advanced Biotechnologies (CHAB), ATeNCenter, University of Palermo, 90100 Palermo, Italy
5
CEINGE Biotecnologie avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy
The two authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 11 October 2017 / Revised: 27 October 2017 / Accepted: 27 October 2017 / Published: 28 October 2017
(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)
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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. View Full-Text
Keywords: α,β-poly-(N-2-hydroxyethyl)-d,l-aspartamide (PHEA); poly(lactic acid) (PLA); poly(ethylene glycol) (PEG); polymeric nanoparticles; margination α,β-poly-(N-2-hydroxyethyl)-d,l-aspartamide (PHEA); poly(lactic acid) (PLA); poly(ethylene glycol) (PEG); polymeric nanoparticles; margination
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Craparo, E.F.; D’Apolito, R.; Giammona, G.; Cavallaro, G.; Tomaiuolo, G. Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure. Molecules 2017, 22, 1845.

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