title: Red blood cells affect the margination of microparticles in synthetic microcapillaries and intravital microcirculation as a function of their size and shape.
abstract: A key step in particle-based drug delivery throughmicrocirculation is particlemigration from blood flow to vesselwalls, also known as “margination”,which promotes particle contact and adhesion to the vesselwall. Margination and adhesion should be independently addressed as two distinct phenomena, considering that the former is a fundamental prerequisite to achieve particle adhesion and subsequent extravasation. Although margination has beenmodeled by numerical simulations and investigated inmodel systems in vitro, experimental studies including red blood cells (RBCs) are lacking. Here, we evaluate the effect of RBCs on margination through microfluidic studies in vitro and by intravital microscopy in vivo.We showthatmargination,which is almost absent when particles are suspended in a cell-free medium, is drastically enhanced by RBCs. This effect is size- and shape-dependent, larger spherical/discoid particles being more effectively marginated both in vitro and in vivo. Our findings can be explained by the collision of particles with RBCs that induces the drifting of the particles towards the vessel walls where they become trapped in the cell-free layer. These results are relevant for the design of drug delivery strategies based on systemically administered carriers.
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, Italy; CEINGE Biotecnologie avanzate, Napoli, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: D'Apolito
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, Italy; CEINGE Biotecnologie avanzate, Napoli, Italy. Electronic address: g.tomaiuolo@unina.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tomaiuolo
authors.affiliation: Department of NanoMedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.affiliation: Department of NanoMedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Minardi
authors.affiliation: Department of NanoMedicine, Houston Methodist Research Institute, Houston, TX, USA; Naval Medical Research Unit, San Antonio, TX, USA.
authors.forename: Dickson
authors.initials: D
authors.lastname: Kirui
authors.affiliation: Department of NanoMedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Università di Napoli Federico II, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Cevenini
authors.affiliation: Department of NanoMedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Palomba
authors.affiliation: Department of NanoMedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Università di Napoli Federico II, Italy; CEINGE Biotecnologie avanzate, Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.affiliation: Department of NanoMedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, Italy; CEINGE Biotecnologie avanzate, Napoli, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Guido
mesh_terms: D000818:Animals; D002196:Capillaries / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008822:Mice, Transgenic; D008833:Microcirculation; D044085:Microfluidics; D018613:Microscopy, Confocal; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Drug delivery; Margination; Micro-particles; Microcirculation; Red blood cells; Shape; Size