Drug carriers for vascular drug delivery

Koren, Erez; Torchilin, Vladimir P.

doi:10.1002/iub.496

Cited by 33 publications

(17 citation statements)

References 44 publications

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“…The situation is the same with nanomaterials if they need to carry the drug toward cells located outside the blood compartment. As crossing the endothelium might be an obstacle, few nanoparticle-based strategies have considered the possibility to target endothelial cells that can express specific markers of different pathologies [63]. When the integrity of blood vessels is dramatically affected by the pathological process and the endothelium becomes leaky because of the appearance of fenestrations, nanomaterials of small enough size can diffuse out of the compartment hence in the tissue to reach target cells.…”

Section: Ongoing Research and Discussion On The Use Of Nanomaterialsmentioning

confidence: 99%

Nanomaterials: Applications in Drug Delivery

Vauthier

Couvreur

Fattal

2012

Nanomaterials: A Danger or a Promise?

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Soon after the discovery of liposomes by Bangham in 1966 (Bangham et al. 1969, nanomaterials were introduced in medicine and the development of the first polymer nanoparticles for oral administration was achieved by Speiser in the late 1960s (Khanna and Speiser 1969). In the early 1970s, these objects were considered as the possible ''magic bullet'' that was a concept proposed 60 years before by the Nobel Prize laureate in Medicine Paul Ehrlich. The aim of the magic bullet is to improve treatments by targeting drugs to diseased tissues cells and subcellular compartments (Kreuter 2007). The introduction of nanomaterials in drug formulation strategies became sources of major innovations in drug delivery over the last 40 years (Couvreur and Vauthier 2006;Kreuter 2007;Bosch and Rosich 2008). IntroductionSoon after the discovery of liposomes by Bangham in 1966 [12], nanomaterials were introduced in medicine and the development of the first polymer nanoparticles for oral administration was achieved by Speiser in the late 1960s [62]. In the early 1970s, these objects were considered as the possible ''magic bullet'' that was a concept proposed 60 years before by the Nobel Prize laureate in Medicine Paul Ehrlich. The aim of the magic bullet is to improve treatments by targeting drugs to diseased tissues cells and subcellular compartments [64]. The introduction of nanomaterials in drug formulation strategies became sources of major innovations in drug delivery over the [26] were on the basis of key achievements in the early ages of the nanomedicine leading to major progresses and the marketing of a new generation of drug formulations [2,53,78,83,93,101,116,119]. At present, a myriad of nanomaterials are considered as suitable nanomedicines [1,36,93]. They have emerged from polymer chemistry and from a better understanding of mechanisms governing molecules self-assembling properties which allowed the development of many types of nano-objects according to a bottom-up approach. Most advanced developments are intended to design multifunctional nanomaterials helping the diagnostic and at the same time, if necessary, the delivery of the right amount of drug on demand and at the right place [36,118].It is noteworthy that any developments that concern medicines applied to human and animals are submitted to a strong regulation. Risks are taken into consideration at the root of developments and many projects are aborted in their earlier age because of safety problems. During development of pharmaceutics, the benefice to risk balance needs to be proved and must satisfy stringent requirements imposed by rules of agencies in charge of authorizations for marketing of the new drug products. Obviously, developments of new medicines using nanomaterials are concerned by these rules. However, in the absence of sufficient knowledge on nanomaterials regarding their safety and protocols of evaluation, drugs formulated in nanotechnologies are currently still developed on the basis of regulations in use for conventional drugs. Regulato...

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Section: Ongoing Research and Discussion On The Use Of Nanomaterialsmentioning

confidence: 99%

Nanomaterials: Applications in Drug Delivery

Vauthier

Couvreur

Fattal

2012

Nanomaterials: A Danger or a Promise?

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“…This can be considered the first step in cardiovascular disease, this is especially important as the endothelial dysfunction may be reversible at this point. ENM deposition within this layer would allow for direct cell-ENM interaction, possibly resulting in an increase in reactive oxygen species, localized oxidative stress, and oxidative scavenge 15 . A primary mediator is nitric oxide gas (NO), an endothelium-derived hyperpolarizing factor widely considered a primary regulator of vascular reactivity.…”

Section: Cardiovascular Systemmentioning

confidence: 99%

Vascular distribution of nanomaterials

Stapleton

Nurkiewicz

2014

WIREs Nanomed Nanobiotechnol

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Once considered primarily occupational, novel nanotechnology innovation and application has led to widespread domestic use and intentional biomedical exposures. With these exciting advances, the breadth and depth of toxicological considerations must also be expanded. The vascular system interacts with every tissue in the body, striving to homeostasis. Engineered nanomaterials (ENM) have been reported to distribute in many different organs and tissues. However, these observations have tended to use approaches requiring tissue homogenization and/or gross organ analyses. These techniques, while effective in establishing presence, preclude an exact determination of where ENM are deposited within a tissue. It is necessary to identify this exact distribution and deposition of ENM throughout the cardiovascular system, with respect to vascular hemodynamics and in vivo/ in vitro ENM modifications taken into account if nanotechnology is to achieve its full potential. Distinct levels of the vasculature will first be described as individual compartments. Then the vasculature will be considered as a whole. These unique compartments and biophysical conditions will be discussed in terms of their propensity to favor ENM deposition. Understanding levels of the vasculature will also be discussed. Ultimately, future studies must verify the mechanisms speculated on and presented herein.

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“…Based on the natural molecular interaction occurring during inflammation between leukocyte and EC, vascular‐targeted carriers (VTCs) that target activated ECs have been sought and developed (Figure b) as a potent drug delivery strategy . Briefly, the active targeting of VTCs is based on functionalizing these carriers with ligands and antibodies that enable specific ligand‐receptor pairing with their complimentary overexpressed inflammatory receptors on the EC .…”

Section: Introductionmentioning

confidence: 99%

Targeting functionalized nanoparticles to activated endothelial cells under high wall shear stress

Zukerman

Khoury

Shammay

et al. 2019

Bioengineering & Transla Med

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Local inflammation of the endothelium is associated with a plethora of cardiovascular diseases. Vascular-targeted carriers (VTCs) have been advocated to provide focal effective therapeutics to these disease sites. Here, we examine the design of functionalized nanoparticles (NPs) as VTCs that can specifically localize at an inflamed vessel wall under pathological levels of high shear stress, associated for example with clinical (or in vivo) conditions of vascular narrowing and arteriogenesis. To test this, carboxylated fluorescent 200 nm polystyrene particles were functionalized with ligands to activated endothelium, that is, an E-selectin binding peptide (Esbp), an anti ICAM-1 antibody, or using a combination of both. The functionalized NPs were investigated in vitro using microfluidic models lined with inflamed (TNF-α stimulated) and control endothelial cells (EC).Specifically, their adhesion was monitored under different relevant wall shear stresses (i.e., 40-300 dyne/cm 2 ) via real-time confocal microscopy. Experiments reveal a significantly higher specific adhesion of the examined functionalized NPs to activated EC for the window of examined wall shear stresses. Moreover, particle adhesion correlated with the surface coating density whereby under high surface coating (i.e.,~10,000 molecule/particle), shear-dependent particle adhesion increased significantly. Altogether, our results show that functionalized NPs can be designed to target inflamed endothelial cells under high shear stress. Such VTCs underscore the potential for attractive avenues in targeting drugs to vasoconstriction and arteriogenesis sites. K E Y W O R D S drug delivery, endothelium, inflammation, microfluidics, shear stress, vascular-targeted carriers (VTCs)

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Drug carriers for vascular drug delivery

Cited by 33 publications

References 44 publications

Nanomaterials: Applications in Drug Delivery

Nanomaterials: Applications in Drug Delivery

Vascular distribution of nanomaterials

Targeting functionalized nanoparticles to activated endothelial cells under high wall shear stress

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