The role of the cell surface glycocalyx in drug delivery to and through the endothelium

Fu, Lu; Kim, Hana; Sterling, James D.; Baker, Shenda M.; Lord, Megan S.

doi:10.1016/j.addr.2022.114195

Cited by 20 publications

(16 citation statements)

References 182 publications

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“…Prior studies also emphasized the significant role of the vascular endothelial glycocalyx in molecular transport . We further investigated the difference in the glycocalyx-related genes between the BBB transwell and BBB Chip.…”

Section: Resultsmentioning

confidence: 99%

“…28 Importantly, it plays a significant role as a molecular transport regulator in endothelial cells. 25,29,30 The crucial difference between the BBB transwell and BBB Chip lies in fluid flow, which mimics in vivo blood circulation, while other factors such as volume-to-area ratio, oxygen, and nutrient transportation also vary. 31−33 To explore whether fluid flow is a critical factor responsible for replicating the endothelial glycocalyx in mBECs, 34 we investigated the change in endothelial glycocalyx in the BBB Chip under both fluidic and static conditions (Figure 4a).…”

Section: Development Of the Mouse Bbb Transwell Andmentioning

confidence: 99%

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Organ-on-a-Chip Approach for Accelerating Blood–Brain Barrier Nanoshuttle Discovery

Choi,

Kim,

Mukhambetiyar

et al. 2024

ACS Nano

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Organ-on-a-chip, which recapitulates the dynamics of in vivo vasculature, has emerged as a promising platform for studying organ-specific vascular beds. However, its practical advantages in identifying vascular-targeted drug delivery systems (DDS) over traditional in vitro models remain underexplored. This study demonstrates the reliability and efficacy of the organ-on-a-chip in screening efficient DDS by comparing its performance with that of a conventional transwell, both designed to simulate the blood–brain barrier (BBB). The BBB nanoshuttles discovered through BBB Chip-based screening demonstrated superior functionality in vivo compared to those identified using transwell methods. This enhanced effectiveness is attributed to the BBB Chip’s accurate replication of the structure and dynamics of the endothelial glycocalyx, a crucial protective layer within blood vessels, especially under shear stress. This capability of the BBB Chip has enabled the identification of molecular shuttles that efficiently exploit the endothelial glycocalyx, thereby enhancing transendothelial transport efficacy. Our findings suggest that organ-on-a-chip technology holds considerable promise for advancing research in vascular-targeted DDS due to its accurate simulation of molecular transport within endothelial systems.

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Section: Resultsmentioning

confidence: 99%

Section: Development Of the Mouse Bbb Transwell Andmentioning

confidence: 99%

Organ-on-a-Chip Approach for Accelerating Blood–Brain Barrier Nanoshuttle Discovery

Choi,

Kim,

Mukhambetiyar

et al. 2024

ACS Nano

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“…Increased BBB permeability leads to an influx of pro-inflammatory cytokines into the brain . The glycocalyx is an important component of the BBB and involved in maintaining vascular permeability and inflammatory responses. − Heparin is known to inhibit the degradation of the glycocalyx and protect it, , and heparin used in the UFH-SPIONs may therefore contribute to their antiepileptic effect by inhibiting neuroinflammation and protecting the BBB structure.…”

Section: Resultsmentioning

confidence: 99%

Heparin-Modified Superparamagnetic Iron Oxide Nanoparticles Suppress Lithium Chloride/Pilocarpine-Induced Temporal Lobe Epilepsy in Rats through Attenuation of Inflammation and Oxidative Stress

Xu,

Wang,

et al. 2024

ACS Chem. Neurosci.

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The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood−brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1β, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.

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“…The evidence for the charge barrier of the CAM glycocalyx is based on biochemical composition and interactions. In most tissues, the glycocalyx is rich in glycosaminoglycans like heparan sulfate, chondroitin sulfate, and hyaluronic acid [ 18 , 19 ]. These molecules have repeating disaccharide units that contain negatively charged groups such as sulfate and carboxylate ions.…”

Section: Discussionmentioning

confidence: 99%

Facilitated Transport across Glycocalyceal Barriers in the Chick Chorioallantoic Membrane

Dayal,

Pan,

Kwan

et al. 2023

Polymers

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Targeted drug delivery to visceral organs offers the possibility of not only limiting the required dose, but also minimizing drug toxicity; however, there is no reliable method for delivering drugs to the surface of visceral organs. Here, we used six color tracers and the chick chorioallantoic membrane (CAM) model to investigate the use of the heteropolysaccharide pectin to facilitate tracer diffusion across the glycocalyceal charge barrier. The color tracers included brilliant blue, Congo red, crystal violet, indocyanine green, methylene blue, and methyl green. The direct application of the tracers to the CAM surface or embedding tracers into linear-chain nanocellulose fiber films resulted in no significant diffusion into the CAM. In contrast, when the tracers were actively loaded into branched-chain pectin films, there was significant detectable diffusion of the tracers into the CAM. The facilitated diffusion was observed in the three cationic tracers but was limited in the three anionic tracers. Diffusion appeared to be dependent on ionic charge, but independent of tracer size or molecular mass. We conclude that dye-loaded pectin films facilitated the diffusion of color tracers across the glycocalyceal charge barrier and may provide a therapeutic path for drug delivery to the surface of visceral organs.

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The role of the cell surface glycocalyx in drug delivery to and through the endothelium

Cited by 20 publications

References 182 publications

Organ-on-a-Chip Approach for Accelerating Blood–Brain Barrier Nanoshuttle Discovery

Organ-on-a-Chip Approach for Accelerating Blood–Brain Barrier Nanoshuttle Discovery

Heparin-Modified Superparamagnetic Iron Oxide Nanoparticles Suppress Lithium Chloride/Pilocarpine-Induced Temporal Lobe Epilepsy in Rats through Attenuation of Inflammation and Oxidative Stress

Facilitated Transport across Glycocalyceal Barriers in the Chick Chorioallantoic Membrane

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