Polyglycerols as Multi-Functional Platforms: Synthesis and Biomedical Applications

Pouyan, Paria; Cherri, Mariam; Haag, Rainer

doi:10.3390/polym14132684

Cited by 23 publications

(32 citation statements)

References 121 publications

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“…Dendritic PGs with different terminal groups were extensively studied by Haag’s group. ,,,− The preparation of linear PG was carried out using anionic polymerization according to the previously published method by Carlotti et al To afford the finalized therapeutic polymers, the pendant alcohol groups were modified. For LPG-Sulf, the polymer was sulfated using the sulfur trioxide pyridine complex and for LPG-Sia, alkyne groups were introduced to allow for copper azide alkyne cycloaddition of azide-containing clickable 2,3 sialyl oligosaccharides.…”

Section: Resultsmentioning

confidence: 99%

Sulfated Hyperbranched and Linear Polyglycerols Modulate HMGB1 and Morphological Plasticity in Neural Cells

Maysinger

Zhang

et al. 2023

ACS Chem. Neurosci.

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The objective of this study was to establish if polyglycerols with sulfate or sialic acid functional groups interact with high mobility group box 1 (HMGB1), and if so, which polyglycerol could prevent loss of morphological plasticity in excitatory neurons in the hippocampus. Considering that HMGB1 binds to heparan sulfate and that heparan sulfate has structural similarities with dendritic polyglycerol sulfates (dPGS), we performed the experiments to show if polyglycerols can mimic heparin functions by addressing the following questions: (1) do dendritic and linear polyglycerols interact with the alarmin molecule HMGB1? (2) Does dPGS interaction with HMGB1 influence the redox status of HMGB1? (3) Can dPGS prevent the loss of dendritic spines in organotypic cultures challenged with lipopolysaccharide (LPS)? LPS plays a critical role in infections with Gram-negative bacteria and is commonly used to test candidate therapeutic agents for inflammation and endotoxemia. Pathologically high LPS concentrations and other stressful stimuli cause HMGB1 release and post-translational modifications. We hypothesized that (i) electrostatic interactions of hyperbranched and linear polysulfated polyglycerols with HMGB1 will likely involve sites similar to those of heparan sulfate. (ii) dPGS can normalize HMGB1 compartmentalization in microglia exposed to LPS and prevent dendritic spine loss in the excitatory hippocampal neurons. We performed immunocytochemistry and biochemical analyses combined with confocal microscopy to determine cellular and extracellular locations of HMGB1 and morphological plasticity. Our results suggest that dPGS interacts with HMGB1 similarly to heparan sulfate. Hyperbranched dPGS and linear sulfated polymers prevent dendritic spine loss in hippocampal excitatory neurons. MS/MS analyses reveal that dPGS-HMGB1 interactions result in fully oxidized HMGB1 at critical cysteine residues (Cys23, Cys45, and Cys106). Triply oxidized HMGB1 leads to the loss of its proinflammatory action and could participate in dPGS-mediated spine loss prevention. LPG-Sia exposure to HMGB1 results in the oxidation of Cys23 and Cys106 but does not normalize spine density.

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Section: Resultsmentioning

confidence: 99%

Sulfated Hyperbranched and Linear Polyglycerols Modulate HMGB1 and Morphological Plasticity in Neural Cells

Maysinger

Zhang

et al. 2023

ACS Chem. Neurosci.

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“…Highly reduced conductive graphene nanoinks (HRG-HPGS) with hyperbranched polyglycerol and PCL nanofibers showed enhanced electrical conductivity and in vitro cell compatibility with stem cells . HPG polymers were explored for a plethora of biomedical applications, and their possibilities of modification or functionalization with different polymers were described. ,− …”

Section: Introductionmentioning

confidence: 99%

Controlled Synthesis of Dendrite-like Polyglycerols Using Aluminum Complex for Biomedical Applications

et al. 2023

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This work describes a one-pot synthesis of dendrite-like hyperbranched polyglycerols (HPGs) via a ring-opening multibranching polymerization (ROMBP) process using a bis(5,7-dichloro-2-methyl-8-quinolinolato)methyl aluminum complex ( 1 ) as a catalyst and 1,1,1-tris(hydroxymethyl)propane/trimethylol propane (TMP) as an initiator. Single-crystal X-ray diffraction (XRD) analysis was used to elucidate the molecular structure of complex 1 . Inverse-gated (IG) 13 C NMR analysis of HPGs showed degree of branching between 0.50 and 0.57. Gel permeation chromatography (GPC) analysis of the HPG polymers provided low, medium, and high-molecular weight ( M n ) polymers ranging from 14 to 73 kDa and molecular weight distributions ( M w / M n ) between 1.16 and 1.35. The obtained HPGs exhibited high wettability with water contact angle between 18 and 21° and T g ranging between −39 and −55 °C. Notably, ancillary ligand-supported aluminum complexes as catalysts for HPG polymerization reactions have not been reported to date. The obtained HPG polymers in the presence of the aluminum complex ( 1 ) can be used for various biomedical applications. Here, nanocomposite electrospun fibers were fabricated with synthesized HPG polymer. The nanofibers were subjected to cell culture experiments to evaluate cytocompatibility behavior with L929 and MG63 cells. The cytocompatibility studies of HPG polymer and nanocomposite scaffold showed high cell viability and spreading. The study results concluded, synthesized HPG polymers and composite nanofibers can be used for various biomedical applications.

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“…Hyperbranched polyglycerols (HPGs) have been explored as a building block in developing materials for biomedical applications [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. The great interest by scientists in this polymer is due to its biocompatibility, non-immunogenic nature, good water solubility, versatility and high end-group functionality provided by its hyperbranched structure [ 19 , 21 , 22 , 23 , 24 , 25 ]. Moreover, HPG can be used as a substitute for PEG (polyethylene glycol) [ 22 ], due to their similarity, and they have better resistance to protein adsorption than the latter [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

pH-Sensitive Degradable Oxalic Acid Crosslinked Hyperbranched Polyglycerol Hydrogel for Controlled Drug Release

et al. 2023

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pH-sensitive degradable hydrogels are smart materials that can cleave covalent bonds upon pH variation, leading to their degradation. Their development led to many applications for drug delivery, where drugs can be released in a pH-dependent manner. Crosslinking hyperbranched polyglycerol (HPG), a biocompatible building block bearing high end-group functionality, using oxalic acid (OA), a diacid that can be synthesized from CO2 and form highly activated ester bonds, can generate this type of smart hydrogel. Aiming to understand the process of developing this novel material and its drug release for oral administration, its formation was studied by varying reactant stoichiometry, concentration and cure procedure and temperature; it was characterized regarding gel percent (%gel), swelling degree (%S), FTIR and thermal behavior; impregnated using ibuprofen, as a model drug, and a release study was carried out at pH 2 and 7. Hydrogel formation was evidenced by its insolubility, FTIR spectra and an increase in Td and Tg; a pre-cure step was shown to be crucial for its formation and an increase in the concentration of the reactants led to higher %gel and lower %S. The impregnation resulted in a matrix-encapsulated system; and the ibuprofen release was negligible at pH 2 but completed at pH 7 due to the hydrolysis of the matrix. A pH-sensitive degradable HPG-OA hydrogel was obtained and it can largely be beneficial in controlled drug release applications.

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Polyglycerols as Multi-Functional Platforms: Synthesis and Biomedical Applications

Cited by 23 publications

References 121 publications

Sulfated Hyperbranched and Linear Polyglycerols Modulate HMGB1 and Morphological Plasticity in Neural Cells

Sulfated Hyperbranched and Linear Polyglycerols Modulate HMGB1 and Morphological Plasticity in Neural Cells

Controlled Synthesis of Dendrite-like Polyglycerols Using Aluminum Complex for Biomedical Applications

pH-Sensitive Degradable Oxalic Acid Crosslinked Hyperbranched Polyglycerol Hydrogel for Controlled Drug Release

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