Administration, distribution, metabolism and elimination of polymer therapeutics

Markovsky, Ela; Baabur-Cohen, Hemda; Eldar‐Boock, Anat; Omer, L. M. O.; Tiram, Galia; Ferber, Shiran; Ofek, Paula; Polyak, Dina; Scomparin, Anna; Satchi‐Fainaro, Ronit

doi:10.1016/j.jconrel.2011.12.021

Cited by 266 publications

(192 citation statements)

References 163 publications

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“…Generally, large molecules of water soluble synthetic polymers can remain in tissue and return to the blood stream by lymphatic circulation. 48 If the molecules are under the glomerular threshold, they will be eliminated by glomerular filtration in the kidneys and will be excreted in the urine. The polymeric chains larger than the renal threshold may be taken by the mononuclear phagocyte system, also known as reticuloendothelial system, as a foreign material.…”

Section: Figurementioning

confidence: 99%

“…The polymeric chains larger than the renal threshold may be taken by the mononuclear phagocyte system, also known as reticuloendothelial system, as a foreign material. [48][49][50] After phagocytosis, the synthetic polymer will be destroyed or sequestered in mononuclear phagocyte system organs. Also the pathway of excreting PEDOT:PSS can be a xenobiotic metabolism in the liver.…”

Section: Figurementioning

confidence: 99%

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3D conductive nanocomposite scaffold for bone tissue engineering

Shahini¹,

Yazdimamaghani²,

Walker³

et al. 2013

IJN

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Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D) ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene) poly(4-styrene sulfonate) (PEDOT:PSS), in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

3D conductive nanocomposite scaffold for bone tissue engineering

Shahini¹,

Yazdimamaghani²,

Walker³

et al. 2013

IJN

View full text Add to dashboard Cite

show abstract

“…On the other hand and as the main drawback, some specific amino acid sequences or homopeptides can trigger disease cascades or their accumulation as aggregates may result in disease promotion, i.e., neurodegeneration disorders. Therefore, this possible impaired toxicity must be studied, and precise control of the selected amino acid composition and the final macromolecular architecture adopted have been defined as crucial design features [35][36][37][38]. It has to be emphasised that there is a growing effort to better understand the structure-activity relationships in order to better define safety and efficacy of these novel therapeutics [15].…”

Section: Introductionmentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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“…The protein corona therefore might interfere with cellular uptake and modify the interaction between particles themselves. Likely, specific proteins of the protein corona influence the tendency of NPs to form aggregates which in turn also influences their biodistribution in vivo [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Aggregation Behavior of Polystyrene-Nanoparticles in Human Blood Serum and its Impact on the in vivo Distribution in Mice

Mohr

Sommer²,

Baier

et al. 2014

J Nanomed Nanotechnol

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The interactions between nanoparticles (NPs) and proteins in complex biological application media such as blood serum are capable of inducing aggregate formation which can lead to subsequent changes in biological activity. Here, we correlate surface charge, aggregation-tendency, and surface serum protein adsorption with cellular uptake and biodistribution in mice.Polystyrene-based NPs (80 -170 nm) with different surface functionalizations were synthesized and incubated with human serum. Interaction of NPs with serum proteins and aggregate formation were analyzed by mass spectrometryanalysis and dynamic light-scattering. Influence of surface functionalization on specific cellular uptake and organdistribution was characterized.Localization and organ targeting of intravenously applied NPs preferentially depended on their aggregationbehavior in the presence of serum. Whereas strongly aggregating particles mainly located to liver, non-aggregating particles distributed to all organs. Determination of aggregate formation of NPs in the presence of serum and further analysis of the protein corona allows for pre-selection of NPs for in vivo application. studies were done by dynamic light scattering applying a previously developed pre-in vivo screening method [10]. This enabled us to analyze the effect of surface functionalization on aggregation and protein binding in the presence of human serum under physiologically relevant conditions. To allow analyzing the cellular uptake of NPs in cells of the peripheral blood as well as in professional antigen-presenting cells, the NPs were fluorescently labeled with boron-dipyrromethene (BODIPY) for flow cytometry and immune fluorescence. In addition, the particles were loaded with a near-infrared dye (IR-Dye 780) for in vivo imaging. Using quantitative high performance liquid chromatography coupled with mass spectrometry, we determined the composition of the protein corona. Using these particles, we were able to demonstrate that the pattern of protein binding in the presence of serum correlates with the tendency to form aggregates in vitro and in vivo. In addition, the charge of the particles' surface influenced their uptake in phagocytes and endocytosis as well as their biodistribution after intravenous application in mice.

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Administration, distribution, metabolism and elimination of polymer therapeutics

Cited by 266 publications

References 163 publications

3D conductive nanocomposite scaffold for bone tissue engineering

3D conductive nanocomposite scaffold for bone tissue engineering

Peptide-Based Polymer Therapeutics

Aggregation Behavior of Polystyrene-Nanoparticles in Human Blood Serum and its Impact on the in vivo Distribution in Mice

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