Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Craparo, Emanuela Fabiola, D’Apolito, Rosa, Giammona, Gaetano, Cavallaro, Gennara, Tomaiuolo, Giovanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150309/
https://www.ncbi.nlm.nih.gov/pubmed/29143777
http://dx.doi.org/10.3390/molecules22111845
_version_ 1783356964379557888
author Craparo, Emanuela Fabiola
D’Apolito, Rosa
Giammona, Gaetano
Cavallaro, Gennara
Tomaiuolo, Giovanna
author_facet Craparo, Emanuela Fabiola
D’Apolito, Rosa
Giammona, Gaetano
Cavallaro, Gennara
Tomaiuolo, Giovanna
author_sort Craparo, Emanuela Fabiola
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6150309
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61503092018-11-13 Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure Craparo, Emanuela Fabiola D’Apolito, Rosa Giammona, Gaetano Cavallaro, Gennara Tomaiuolo, Giovanna Molecules Article 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. MDPI 2017-10-28 /pmc/articles/PMC6150309/ /pubmed/29143777 http://dx.doi.org/10.3390/molecules22111845 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Craparo, Emanuela Fabiola
D’Apolito, Rosa
Giammona, Gaetano
Cavallaro, Gennara
Tomaiuolo, Giovanna
Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure
title Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure
title_full Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure
title_fullStr Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure
title_full_unstemmed Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure
title_short Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure
title_sort margination of fluorescent polylactic acid–polyaspartamide based nanoparticles in microcapillaries in vitro: the effect of hematocrit and pressure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150309/
https://www.ncbi.nlm.nih.gov/pubmed/29143777
http://dx.doi.org/10.3390/molecules22111845
work_keys_str_mv AT craparoemanuelafabiola marginationoffluorescentpolylacticacidpolyaspartamidebasednanoparticlesinmicrocapillariesinvitrotheeffectofhematocritandpressure
AT dapolitorosa marginationoffluorescentpolylacticacidpolyaspartamidebasednanoparticlesinmicrocapillariesinvitrotheeffectofhematocritandpressure
AT giammonagaetano marginationoffluorescentpolylacticacidpolyaspartamidebasednanoparticlesinmicrocapillariesinvitrotheeffectofhematocritandpressure
AT cavallarogennara marginationoffluorescentpolylacticacidpolyaspartamidebasednanoparticlesinmicrocapillariesinvitrotheeffectofhematocritandpressure
AT tomaiuologiovanna marginationoffluorescentpolylacticacidpolyaspartamidebasednanoparticlesinmicrocapillariesinvitrotheeffectofhematocritandpressure