Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions

Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving interven...

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Autores principales:	Lauren B. Grimsley, Phillip C. West, Callie D. McAdams, Charles A. Bush, Stacy S. Kirkpatrick, Joshua D. Arnold, Michael R. Buckley, Raymond A. Dieter, Michael B. Freeman, Michael M. McNally, Scott L. Stevens, Oscar H. Grandas, Deidra J. H. Mountain
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	liposomes targeted drug delivery hemodynamic flow vascular shear stress vascular therapeutics Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/90e4197913bc4138b5ab94f8e72b3c32
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spelling	oai:doaj.org-article:90e4197913bc4138b5ab94f8e72b3c322021-11-25T18:40:53ZLiposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions10.3390/pharmaceutics131118161999-4923https://doaj.org/article/90e4197913bc4138b5ab94f8e72b3c322021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1816https://doaj.org/toc/1999-4923Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics.Lauren B. GrimsleyPhillip C. WestCallie D. McAdamsCharles A. BushStacy S. KirkpatrickJoshua D. ArnoldMichael R. BuckleyRaymond A. DieterMichael B. FreemanMichael M. McNallyScott L. StevensOscar H. GrandasDeidra J. H. MountainMDPI AGarticleliposomestargeted drug deliveryhemodynamic flowvascular shear stressvascular therapeuticsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1816, p 1816 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liposomes targeted drug delivery hemodynamic flow vascular shear stress vascular therapeutics Pharmacy and materia medica RS1-441
spellingShingle	liposomes targeted drug delivery hemodynamic flow vascular shear stress vascular therapeutics Pharmacy and materia medica RS1-441 Lauren B. Grimsley Phillip C. West Callie D. McAdams Charles A. Bush Stacy S. Kirkpatrick Joshua D. Arnold Michael R. Buckley Raymond A. Dieter Michael B. Freeman Michael M. McNally Scott L. Stevens Oscar H. Grandas Deidra J. H. Mountain Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions
description	Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics.
format	article
author	Lauren B. Grimsley Phillip C. West Callie D. McAdams Charles A. Bush Stacy S. Kirkpatrick Joshua D. Arnold Michael R. Buckley Raymond A. Dieter Michael B. Freeman Michael M. McNally Scott L. Stevens Oscar H. Grandas Deidra J. H. Mountain
author_facet	Lauren B. Grimsley Phillip C. West Callie D. McAdams Charles A. Bush Stacy S. Kirkpatrick Joshua D. Arnold Michael R. Buckley Raymond A. Dieter Michael B. Freeman Michael M. McNally Scott L. Stevens Oscar H. Grandas Deidra J. H. Mountain
author_sort	Lauren B. Grimsley
title	Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions
title_short	Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions
title_full	Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions
title_fullStr	Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions
title_full_unstemmed	Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions
title_sort	liposomal nanocarriers designed for sub-endothelial matrix targeting under vascular flow conditions
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/90e4197913bc4138b5ab94f8e72b3c32
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Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions

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