Exploring deformable particles in vascular-targeted drug delivery: Softer is only sometimes better.
Biomaterials
; 124: 169-179, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-28209527
ABSTRACT
The ability of vascular-targeted drug carriers (VTCs) to localize and bind to a targeted, diseased endothelium determines their overall clinical utility. Here, we investigate how particle modulus and size determine adhesion of VTCs to the vascular wall under physiological blood flow conditions. In general, deformable microparticles (MPs) outperformed nanoparticles (NPs) in all experimental conditions tested. Our results indicate that MP modulus enhances particle adhesion in a shear-dependent manner. In low shear human blood flow profiles in vitro, low modulus particles showed favorable adhesion, while at high shear, rigid particles showed superior adhesion. This was confirmed in vivo by studying particle adhesion under venous shear profiles in a mouse model of mesenteric inflammation, where MP adhesion was 127% greater (p < 0.0001) for low modulus particles compared to more rigid ones. Mechanistically, we establish that particle collisions with leukocytes drive these trends, rather than differences in particle deformation, localization, or detachment. Overall, this work demonstrates the importance of VTC modulus as a design parameter for enhanced VTC interaction with vascular walls, and thus, contributes important knowledge for development of successful clinical theranostics with applications for many diseases.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Análisis Químico de la Sangre
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Cápsulas
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Endotelio Vascular
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Hidrogeles
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Nanocápsulas
Límite:
Animals
Idioma:
En
Revista:
Biomaterials
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos