Heparin-Superparamagnetic Iron Oxide Nanoparticles for Theranostic Applications.

In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were engineered with an organic coating composed of low molecular weight heparin (LMWH) and bovine serum albumin (BSA), providing heparin-based nanoparticle systems (LMWH@SPIONs). The purpose was to merge the properties of the heparin skeleton and an inorganic core to build up a targeted theranostic nanosystem, which was eventually enhanced by loading a chemotherapeutic agent. Iron oxide cores were prepared via the co-precipitation of iron salts in an alkaline environment and oleic acid (OA) capping.

Suspended Multifunctional Nanocellulose as Additive for Mortars.

Cellulose derivatives have found significant applications in composite materials, mainly because of the increased mechanical performance they ensure. When added to cement-based materials, either in the form of nanocrystals, nanofibrils or micro/nanofibers, cellulose acts on the mixture with fresh and hardened properties, affecting rheology, shrinkage, hydration, and the resulting mechanical properties, microstructure, and durability. Commercial cotton wool was selected as starting material to produce multifunctional nanocelluloses to test as additives for mortars.

Nanocellulose from Cotton Waste and Its Glycidyl Methacrylate Grafting and Allylation: Synthesis, Characterization and Adsorption Properties.

Nanocellulose (NC) is getting ahead as a renewable, biodegradable and biocompatible biomaterial. The NCs for this study were recovered from industrial cotton waste (CFT) by acid hydrolysis (HNC) and by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidation (ONC). They were functionalized by radical based glycidyl methacrylate (GMA) grafting providing crystalline HNC-GMA and ONC-GMA, and by allylation (ALL) providing amorphous HNC-ALL and ONC-ALL.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-7.

Breakthroughs in Medicinal Chemistry [...

Non-Anticoagulant Heparins as Heparanase Inhibitors.

The chapter will review early and more recent seminal contributions to the discovery and characterization of heparanase and non-anticoagulant heparins inhibiting its peculiar enzymatic activity. Indeed, heparanase displays a unique versatility in degrading heparan sulfate chains of several proteoglycans expressed in all mammalian cells. This endo-β-D-glucuronidase is overexpressed in cancer, inflammation, diabetes, atherosclerosis, nephropathies and other pathologies.

In-depth structural characterization of pentosan polysulfate sodium complex drug using orthogonal analytical tools.

Rapid advances have been made in developing analytical technologies for characterization of highly heterogeneous active ingredients of complex drugs, such as pentosan polysulfate (PPS), active ingredient of the drug Elmiron®, approved by the Food and Drug Administration and marketed in the United States to treat interstitial cystitis. PPS sulfated polysaccharides comprise of a repeat unit of β(1-4)-D-xylopyranoses randomly substituted by 4-O-methyl-glucopyranosyluronic acid. To define the critical quality attributes (CQAs) of such a complex drug, it is critical to develop an approach that integrates data from orthogonal analytical methodologies.

Bacterial Nanocellulose and Its Surface Modification by Glycidyl Methacrylate and Ethylene Glycol Dimethacrylate. Incorporation of Vancomycin and Ciprofloxacin.

Among nanocelluloses, bacterial nanocellulose (BNC) has proven to be a promising candidate in a range of biomedical applications, from topical wound dressings to tissue-engineering scaffolds. Chemical modifications and incorporation of bioactive molecules have been obtained, further increasing the potential of BNC. This study describes the incorporation of vancomycin and ciprofloxacin in BNC and in modified BNC to afford bioactive BNCs suitable for topical wound dressings and tissue-engineering scaffolds.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes⁻4.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal . [..

β-Chitin samples with similar microfibril arrangement change mechanical properties varying the degree of acetylation.

Chitin is widespread in nature and is increasingly used in synthetic process for the production of new biomaterials. Chitin degree of acetylation, crystalline structure and microfibril arrangement differentiate chemical, physical and mechanical properties. Nevertheless, no information are available on the relationship between the mechanical properties and the degree of acetylation (DA) in chitin samples in which the microfibril arrangement does not change.

Structure and Function of Stony Coral Intraskeletal Polysaccharides.

Polysaccharides represent a main weight fraction of the intraskeletal organic matrix of corals, but their structure, as well as their function in the calcification process, has been poorly investigated. This communication shows by a combination of techniques (nuclear magnetic resonance, Fourier transform infrared, and monosaccharide composition) that their key component is a 1→3 β-d glucuronic acid polymer and evidences its influence in vitro in the calcification process.

Looking Forward to the Future of Heparin: New Sources, Developments and Applications.

The seven reviews and the eleven articles in this special issue provide an updated survey of recent research and developments in the ever-growing field of heparin, along with low molecular weight heparins (LMWHs) and glycosaminoglycans (GAGs).

Remembering Professor Benito Casu (1927-2016).

Heparin and related drugs have contributed in so many different ways to the drug discovery process, and have provided a platform to understand the pathophysiology of vascular and inflammatory diseases for nearly 100 years.

Structural Characterization of the Low-Molecular-Weight Heparin Dalteparin by Combining Different Analytical Strategies.

A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin by LC-MS and NMR applied both to the whole drug and to its enzymatic products.

Increased migration of antigen presenting cells to newly-formed lymphatic vessels in transplanted kidneys by glycol-split heparin.

Background: Chronic renal transplant dysfunction is characterized by loss of renal function and tissue remodeling, including chronic inflammation and lymph vessel formation. Proteoglycans are known for their chemokine presenting capacity. We hypothesize that interruption of the lymphatic chemokine-proteoglycan interaction interferes with the lymphatic outflow of leukocytes from the renal graft and might decrease the anti-graft allo-immune response.

Characterization of PF4-Heparin Complexes by Photon Correlation Spectroscopy and Zeta Potential.

Heparin-induced thrombocytopenia (HIT) is associated with antibodies to complexes between heparin and platelet factor 4 (PF4), a basic protein usually found in platelet alpha granules. Heparin-induced thrombocytopenia antibodies preferentially recognize macromolecular complexes formed between positively charged PF4 and polyanionic heparins over a narrow range of molar ratios. The aim of this work was to study the complexes that human PF4 forms with heparins from various species, such as porcine, bovine, and ovine; heparins from various organs, such as mucosa and lung; and different low-molecular-weight heparins (LMWHs) at several stoichiometric ratios to evaluate their sizes and charges by photo correlation spectroscopy and zeta potential measurements.

Qualification of HSQC methods for quantitative composition of heparin and low molecular weight heparins.

An NMR HSQC method has recently been proposed for the quantitative determination of the mono- and disaccharide subunits of heparin and low molecular weight heparins (LMWH). The focus of the current study was the validation of this procedure to make the 2D-NMR method suitable for pharmaceutical quality control applications. Pre-validation work investigated the effects of several experimental parameters to assess robustness and to optimize critical factors.

Investigating Glycol-Split-Heparin-Derived Inhibitors of Heparanase: A Study of Synthetic Trisaccharides.

Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS () and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS () from glucose.

Heparin centenary - an ever-young life-saving drug.

On the centenary of the discovery of heparin, the International Journal of Cardiology agreed to publish a collection of mini reviews that summarize the historical development of this ever-young life-saving drug. The present articles deal not only with the historical milestones, but also with current and future perspectives regarding the development of heparin in terms of its structure, as well as on-going biochemical, biological and clinical research. Attention is focused on recent applications of heparin derivatives to non-anticoagulant or antithrombotic therapies, providing particular emphasis on their inhibitory activities, including their potential as anti-cancer agents.

Structural peculiarity and antithrombin binding region profile of mucosal bovine and porcine heparins.

The major compositional differences between bovine mucosal heparin (BMH) and the currently employed porcine mucosal heparin (PMH) have been reported to essentially consist of reduced 6-O-sulfation of the glucosamine residues in BMH and somewhat lower 2-O-sulfation of the iduronate residues in PMH. The present work is based on direct comparison of several BMH and PMH commercial preparations. A combined study by 2D (heteronuclear single quantum coherence, HSQC) NMR and ion-pair reversed-phase high performance liquid chromatography (IPRP-HPLC) coupled with electrospray ionization mass spectrometry (ESI-MS) on the heparins, extended to the analysis of their heparinases digests and fractions separated by affinity chromatography on antithrombin (AT), confirmed the previously reported lower degree of 6-O-sulfation and showed lower 3-O-sulfated glucosamine content in BMH.

Differentiation of generic enoxaparins marketed in the United States by employing NMR and multivariate analysis.

The U.S. Food and Drug Administration defines criteria for the equivalence of Enoxaparin with Lovenox, comprising the equivalence of physiochemical properties, heparin source material and mode of depolymerization, disaccharide building blocks, fragment mapping and sequence of oligosaccharide species, biological and biochemical assays, and in vivo pharmacodynamic profile.

Determination of the molecular weight of low-molecular-weight heparins by using high-pressure size exclusion chromatography on line with a triple detector array and conventional methods.

The evaluation of weight average molecular weight (Mw) and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs). As the most commonly used method for the measurement of such parameters is high performance size exclusion chromatography (HP-SEC), the soundness of results mainly depends on the appropriate calibration of the chromatographic columns used. With the aim of meeting the requirement of proper Mw standards for LMWHs, in the present work the determination of molecular weight parameters (Mw and Mn) by HP-SEC combined with a triple detector array (TDA) was performed.

Susceptibility of enoxaparin reducing end amino sugars to periodate oxidation.

There is a growing interest on glycol-split low-molecular weight heparins (gs-LMWHs), obtained by periodate oxidation of LMWHs, optionally followed by borohydride reduction, as potential anticancer and anti-inflammatory drugs. However, their structural characterization is still a challenging task, mainly because of the high microheterogeneity of the starting material. In addition, susceptibility to oxidation of some end-groups of LMWHs induces additional heterogeneity, making analysis of gs-LMWHs more complex.

Glycosaminoglycans: anticoagulant and nonanticoagulant actions: a short history of symposia held at villa vigoni.

Heparin, a sulfated polysaccharide belonging to the family of glycosaminoglycans, was discovered in the beginning of the 20th century and was initially identified as a procoagulant isolated from liver tissue. After the first application in patients approximately 30 years later, further purification identified the major as well as minor, but important, component units of the complex chain mixtures constituting heparin and the multiplex actions became a scientific challenge recently. A series of "Glycosaminoglycan symposium-anticoagulant and nonanticoagulant actions" developed over the past 20 years and focused on this topic has published research data in three issues of Seminars in Thrombosis & Hemostasis and in several other international scientific journals.

Antithrombin-binding oligosaccharides: structural diversities in a unique function?

Heparin-antithrombin interaction is one of the most documented examples of heparin/protein complexes. The specific heparin sequence responsible for the binding corresponds to a pentasaccharide sequence with an internal 3-O-sulfated glucosamine residue. Moreover, the position of the pentasaccharide along the chain as well as the structure of the neighbor units affects the affinity to antithrombin.