The use of shear stress for targeted drug delivery

Saxer, Till; Müller, Bert

doi:10.1093/cvr/cvt102

Cited by 77 publications

(61 citation statements)

References 50 publications

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“…This difference could be a better physical/mechanical signal to trigger drug release in arteries in comparison with other biological or chemical stimuli. 212 Cardiovascular diseases such as stenosis and atherosclerosis could be promising applications of these endogenous mechano-stimuli-responsive systems. For example a study prepared lenticular liposomes that were stable under static conditions but unstable in the elevated shear stress of atherosclerosis.…”

Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

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New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

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Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

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“…2,3 One strategy involves targeting the constricted arteries by capitalizing on the endogenous, elevated shear stresses present in diseased artery segments and using the changes as a purely physical trigger for drug release. 4 Liposomes composed of the artificial phospholipid Pad-PC-Pad can release their payload in areas of increased shear stress. 5 In order to push this development towards clinical application, the liposomes need to be further characterized to exclude non-desired systemic effects.…”

mentioning

confidence: 99%

Surprising lack of liposome-induced complement activation by artificial 1,3-diamidophospholipids in vitro

Bugna

Buscema

Matviykiv

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Cardio-vascular diseases are the main cause of death, emphasizing the need to improve patient treatment and survival. One therapeutic approach is a liposome-based drug carrier system specifically targeting constricted arteries. The recently discovered mechano-sensitive liposomes use hemodynamic shear-stress differences between healthy and constricted blood vessels as trigger for drug release. Liposomes are promising delivery containers but are being recognized as foreign by the immune system. Complement activation as essential factor of the recognition leads to adverse effects. Here, we tested complement activation by liposomes formulated from the artificial phospholipid Pad-PC-Pad in vitro. Surprisingly no complement activation was detected in human sera and porcine plasma. In in vivo experiments with three pigs, neither anaphylactic reactions nor other significant hemodynamic changes were observed even at comparably high liposome doses. The pilot study holds promise for an absence of complement-mediated adverse effects of Pad-PC-Pad liposomes in human.From the Clinical Editor: A lot of research has been done on new treatment for cardiovascular diseases. Liposome-based carrier systems have also shown promises. In this article, the authors studied the potential risks of complement activation by liposomes in in-vivo experiments. The absence of complement activation by Pad-PC-Pad liposomes may indicate its use in humans.

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“…Specifically, a remarkable interest is addressed to hemodynamics, due to its fundamental role in determining the biodistribution of drugs or other exogenous molecules after systemic administration [28][29] . The applicative implications in the field of Molecular Imaging are many, ranging from the validation of blood pool imaging contrast agents to image-monitored drug delivery studies requiring ultrasound-induced BBB opening 30 .…”

Section: Discussionmentioning

confidence: 99%

Non-invasive Parenchymal, Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

Giustetto

Filippi

Castano

et al. 2015

JoVE

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Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive performance-competitive means for cortical and internal brain imaging, retaining a significant potential in many neurologic fields.

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The use of shear stress for targeted drug delivery

Cited by 77 publications

References 50 publications

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Surprising lack of liposome-induced complement activation by artificial 1,3-diamidophospholipids in vitro

Non-invasive Parenchymal, Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

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