Glomerular Filtration Barrier

Oddsson, Ásmundur; Patrakka, Jaakko; Tryggvason, Karl

doi:10.1016/b978-0-12-801238-3.00201-4

Cited by 5 publications

(4 citation statements)

References 87 publications

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“…Next, we performed RAFT polymerization to obtain polymers with relative molecular weight below the limit of renal filtration, which is usually between 30 and 50 kDa [ 78 ], but recent results point to a more complex issue [ 79 ]. The polymerization reaction took place in the presence of AIBN as a radical initiator, and dithiobenzoate (CTPA) as chain transfer agent in an acidic solution to produce P(HPMA) and copolymers P(HPMA- co -MMA) and P(HPMA- co -HAO).…”

Section: Resultsmentioning

confidence: 99%

Hydrophilic Copolymers with Hydroxamic Acid Groups as a Protective Biocompatible Coating of Maghemite Nanoparticles: Synthesis, Physico-Chemical Characterization and MRI Biodistribution Study

et al. 2023

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Superparamagnetic iron oxide nanoparticles (SPION) with a “non-fouling” surface represent a versatile group of biocompatible nanomaterials valuable for medical diagnostics, including oncology. In our study we present a synthesis of novel maghemite (γ-Fe2O3) nanoparticles with positive and negative overall surface charge and their coating by copolymer P(HPMA-co-HAO) prepared by RAFT (reversible addition–fragmentation chain-transfer) copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide (HAO). Coating was realized via hydroxamic acid groups of the HAO comonomer units with a strong affinity to maghemite. Dynamic light scattering (DLS) demonstrated high colloidal stability of the coated particles in a wide pH range, high ionic strength, and the presence of phosphate buffer (PBS) and serum albumin (BSE). Transmission electron microscopy (TEM) images show a narrow size distribution and spheroid shape. Alternative coatings were prepared by copolymerization of HPMA with methyl 2-(2-methylprop-2-enoylamino)acetate (MMA) and further post-polymerization modification with hydroxamic acid groups, carboxylic acid and primary-amino functionalities. Nevertheless, their colloidal stability was worse in comparison with P(HPMA-co-HAO). Additionally, P(HPMA-co-HAO)-coated nanoparticles were subjected to a bio-distribution study in mice. They were cleared from the blood stream by the liver relatively slowly, and their half-life in the liver depended on their charge; nevertheless, both cationic and anionic particles revealed a much shorter metabolic clearance rate than that of commercially available ferucarbotran.

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Section: Resultsmentioning

confidence: 99%

Hydrophilic Copolymers with Hydroxamic Acid Groups as a Protective Biocompatible Coating of Maghemite Nanoparticles: Synthesis, Physico-Chemical Characterization and MRI Biodistribution Study

et al. 2023

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“…15 The third and final barrier consists of epithelial podocytes characterized by foot processes that form specialized cell−cell junctions called slit diaphragms that restrict the movement of molecules larger than 40 nm in diameter. 19 In addition, the endothelial cells and epithelial podocytes of the GFB are coated in a layer of proteoglycans called the glycocalyx that can entrap nanoparticles and restrict their passage. Due to these physiological barriers, particles that are less than 10 nm in diameter have generally been reported to cross the GFB most efficiently.…”

Section: Nanomedicine For Kidney Diseasesmentioning

confidence: 99%

“…The intermediate layer is the glomerular basement membrane, a protein-rich matrix of collagen, laminin, and proteoglycans sporting pores less than 10 nm in diameter in a healthy nephron . The third and final barrier consists of epithelial podocytes characterized by foot processes that form specialized cell–cell junctions called slit diaphragms that restrict the movement of molecules larger than 40 nm in diameter . In addition, the endothelial cells and epithelial podocytes of the GFB are coated in a layer of proteoglycans called the glycocalyx that can entrap nanoparticles and restrict their passage.…”

Section: Nanomedicine For Kidney Diseasesmentioning

confidence: 99%

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions

et al. 2023

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Nanoparticles as drug delivery carriers have benefited diseases, including cancer, since the 1990s, and more recently, their promise to quickly and efficiently be mobilized to fight against global diseases such as in the COVID-19 pandemic have been proven. Despite these success stories, there are limited nanomedicine efforts for chronic kidney diseases (CKDs), which affect 844 million people worldwide and can be linked to a variety of genetic kidney diseases. In this Perspective, we provide a brief overview of the clinical status of genetic kidney diseases, background on kidney physiology and a summary of nanoparticle design that enable kidney access and targeting, and emerging technological strategies that can be applied for genetic kidney diseases, including rare and congenital kidney diseases. Finally, we conclude by discussing gaps in knowledge remaining in both genetic kidney diseases and kidney nanomedicine and collective efforts that are needed to bring together stakeholders from diverse expertise and industries to enable the development of the most relevant drug delivery strategies that can make an impact in the clinic.

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“…The foot processes interdigitate with those of adjacent podocytes to form a filtration barrier. Slit diaphragms (basolateral cell junctions ~40 nm in width) between the foot processes are important for the selectivity of the barrier 32 . Approximately 40 signature podocyte genes and proteins that are important for mainte nance of the GFB have been identified, including nephrin (NPHS1), podocin (NPHS2), Wilms tumour protein (WT1) and short transient receptor potential channel 6 (TRPC6) 20,31,33 .…”

Section: The Renal Corpusclementioning

confidence: 99%

Biomimetic models of the glomerulus

et al. 2022

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The use of biomimetic models of the glomerulus has the potential to improve our understanding of the pathogenesis of kidney diseases and to enable progress in therapeutics. Current in vitro models comprise organ-on-a-chip, scaffold-based and organoid approaches. Glomerulus-on-a-chip designs mimic components of glomerular microfluidic flow but lack the inherent complexity of the glomerular filtration barrier. Scaffold-based 3D culture systems and organoids provide greater microenvironmental complexity but do not replicate fluid flows and dynamic responses to fluidic stimuli. As the available models do not accurately model the structure or filtration function of the glomerulus, their applications are limited. An optimal approach to glomerular modelling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. In particular, 3D bioprinting technologies could enable the fabrication of constructs that recapitulate the complex structure of the glomerulus and the glomerular filtration barrier. The next generation of in vitro glomerular models must be suitable for high(er)-content or/and high(er)-throughput screening to enable continuous and systematic monitoring. Moreover, coupling of glomerular or kidney models with those of other organs is a promising approach to enable modelling of partial or full-body responses to drugs and prediction of therapeutic outcomes.

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Glomerular Filtration Barrier

Cited by 5 publications

References 87 publications

Hydrophilic Copolymers with Hydroxamic Acid Groups as a Protective Biocompatible Coating of Maghemite Nanoparticles: Synthesis, Physico-Chemical Characterization and MRI Biodistribution Study

Hydrophilic Copolymers with Hydroxamic Acid Groups as a Protective Biocompatible Coating of Maghemite Nanoparticles: Synthesis, Physico-Chemical Characterization and MRI Biodistribution Study

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions

Biomimetic models of the glomerulus

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