Antithrombic Activity Research Articles

In Vivo Anticoagulant and Antithrombic Activity of Depolymerized Glycosaminoglycan from Apostichopus japonicus and Dynamic Effect-Exposure Relationship in Rat Plasma.

Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa). These glycosaminoglycans markedly prevented thrombosis formation and thrombin-induced platelet aggregation in a dose- and molecular weight-dependent manner in vitro and in vivo. The further bleeding time measurement indicated that DAHG10 exhibited obviously lower hemorrhage risks than native AHG100. Following oral administration, DAHG10 could be absorbed into blood, further dose-dependently prolonging activated partial thromboplastin time (APTT) and thrombin time (TT) as well as inhibiting FXa and FIIa partially through FXase. Anticoagulant activity was positively associated with plasma concentration following oral administration of DAHG10. Our study proposed a new point of view to understand the correlation between effects and exposure of fucosylated chondroitin sulfate as an effective and safe oral antithrombotic agent.

The Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study.

Sodium–glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activation and thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing metformin therapy. The population was divided into two groups: treatment with GLP-1 receptor agonists (GLP-1RA, Group A) and gliflozins (Group B). Oxidative stress, platelet activation and thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline, gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p < 0.001), H2O2 production (−53.4%, p < 0.001), TxB2 (−33.1%, p < 0.001), sP-selectin (−49.3%, p < 0.001) and sCD40L levels (−62.3%, p < 0.001) as well as thrombus formation (−32%, p < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with gliflozins (10–30 μM) showed a reduction in oxidative stress, platelet activation and thrombus growth. Our results showed that gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection.

Antiviral Activities of Pyridine Fused and Pyridine Containing Heterocycles, A Review (from 2000 to 2020).

Heterocyclic compounds play a critical role in medicinal chemistry, and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine, showed various applications, including being an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase in drug resistance, there is an apparent medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display broad biological activities such as anti-microbial, antiviral, antioxidant, anti-diabetic, anti-cancer, anti-malarial, analgesic, and antiinflammatory activities. Furthermore, they display psychopharmacological, antagonistic, anti-amoebic agents, and anti-thrombic activities. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories, including pyridine containing heterocycles and pyridine fused rings. The structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), respiratory syncytial virus (RSV), and cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarized the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing. It is necessary to investigate in vivo and clinical testing for better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and more broad investigations in this field need to be performed.

Optimization of the Composition and Production Technology of Fucoidan Tablets and their Biopharmaceutical Evaluation

The discovery and development of drugs that can compete in effectiveness with direct anticoagulants is a critical problem. Fucoidan is a complex branched heteropolysaccharide with anticoagulant and antithrombic activity. Fucoidan drug substance is hygroscopic and possesses poor technological properties. This study was aimed at development of the optimum composition and technology of fucoidan tablets and their biopharmaceutical evaluation. The generalized Harrington desirability function and dispersion and regression analyses were used for optimization of the fucoidan tablet formulation. The contents of crospovidone and lactose were the most significant factors affecting the disintegration and compressibility of model tablets. The lactose content had the greatest impact on the Carr index and Hausner ratio. The in vitro dissolution curves of the tablets were compared (at pH 1.2, 5.7, and 6.8). The in vitro release of fucoidan from the developed tablets obeyed a first-order kinetic equation.

Endophytic sources of diosgenin, a natural steroid with multiple therapeutic values

Medicinally important steroid-based compound diosgenin is usually obtained from the secondary metabolic products of several plant species. Diosgenin has been proven as a prospective bioactive drug lead to the pharmaceutical industries as having anti-cancer activity, anti-microbial activity, anti-thrombic activity, anti-diabetic activity, cardioprotective activity, anti-inflammatory activity, osteoarthritis protective activity etc. Observing the multiple therapeutic values of this compound, scientists and chemists have become interested to discover alternative sources. Endophytic microorganisms possess the potentials producing prospective secondary metabolites. Some diosgenin producing endophytic fungi and bacteria are detected and reported by authors. Extraction and quantification of the respective secondary metabolite in a proper way is required initially for its large scale production. Regular involvement of advance biotechnological approaches plus industrial fermentation technology along with proper funding following government policy is necessary for further progress in this field. Exploration of a higher number of diosgenin producing endophytic strains will definitely increase the supply for social requisition in a cost-effective and environment-friendly manner as limiting the excessive exploitation of plant sources.

Chemical and pharmacological research on the polyphenol acids isolated from Danshen: A review of salvianolic acids.

Danshen, the dried root of Salvia miltiorrhiza Bge, is a common medicinal herb in Traditional Chinese Medicine, which has been used for the treatment of a number of diseases for thousands of years. More than 2000 years ago, the Chinese early pharmacy monograph "Shennong Materia Medica" recorded that Danshen could be used for the treatment of gastrointestinal diseases, cardiovascular diseases, certain gynecological diseases, etc. Since then, Danshen has been widely used clinically in many different prescriptions for many different diseases, especially for the treatment of cardiovascular diseases. Nowadays, many pharmacological studies about the water-soluble components from Danshen have been reported, especially salvianolic acids. It turned out that salvianolic acids showed strong anti-lipid peroxidation and anti-thrombic activities, and among them, SalAA and SalAB were the most potent. This review focused on the achievements in research of salvianolic acids regarding their bioactivities and pharmacological effects. These studies not only shed light on the water-soluble active components of Danshen and their mechanisms at the molecular level, but also provided theoretical information for the development of new medicines from Danshen for the treatment of cardiovascular and cerebrovascular diseases, inflammatory diseases, metabolic diseases, etc.

Synthesis and Bioactivity Characterization of Scutellarein Sulfonated Derivative.

Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group was introduced at position C-8 of scutellarein (2) to enhance the aqueous solubility of the obtained derivative (3). DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging ability and antithrombic activity were also conducted to determine its bioactivity. The result showed that scutellarein derivate (3) could be a better agent for ischemic cerebrovascular disease treatment.

Tri-layered silk fibroin and poly-ɛ-caprolactone small diameter vascular grafts tested in vitro and in vivo

A silk fibroin (SF) and poly-e-caprolactone (PCL) tri-layered nano-fibrous scaffold composed of an inner, middle, and outer layer is fabricated via sequential electrospinning. The middle layer of the SF/PCL blend nano-fiber is introduced to minimize delamination of each layer of the scaffold. The inner layer is composed of SF with Spirulina maxima extract (SP), and the outer is composed of PCL. The anti-thrombic effects of SP are tested first. The structure, mechanical properties, and cytocompatibility of the scaffold are evaluated. The tri-layered nano-fiber scaffold is implanted into a rat carotid artery, and the sample after 3 weeks of implantation is evaluated histologically. The SP exerts anti-thrombic activity, and the SF with SP inhibits platelet adhesion. The tri-layered scaffold with the middle layer composed of SF/PCL blend exhibits excellent tensile strengths, burst pressure strength, and suture retention strength. The fabricated material does not induce any cytotoxicity. The cells are well spread on the scaffold. Recipient vessel maintains patency 3 weeks after implantation. The inner lumen of the scaffold reveals regenerated endothelial cells. The results indicate that the tri-layered tubular SF/PCL vascular grafts can be used in vascular tissue engineering due to their excellent mechanical properties and good tissue regeneration capability. Open image in new window

Immobilization of anticoagulant-loaded liposomes on cell surfaces by DNA hybridization

An unresolved obstacle in transplantation of islets of Langerhans is the early graft loss caused by thrombotic reactions on the surface of islets after intraportal transplantation. We investigated a versatile method for modifying the surface of islets with liposomes carrying the anticoagulant argatroban using an amphiphilic poly(ethylene glycol)-phospholipid conjugate derivative (PEG-lipid) and DNA hybridization. Argatroban was gradually released from the liposomes on the islets, and antithrombic activity was detected in culture medium. Modified islets retained the ability to control insulin release in response to glucose concentration changes. Although we mainly examined surface modification of islets, this technique may be useful for immobilizing various types of small molecules on cells and tissues and thus may have many applications in cell therapy and regenerative medicine.

Effects of Aqueous Extract of Diospyros Kaki Calyx on Anti-thrombotic Activity in vitro and in vivo

ABSTRACT Objectives：The aim of this study is to research an anti-thrombus effect by Diospyros Kaki Calyx.Methods：The healthy human plasma were gained and used in vitro study such as factor X activity (FXa) inhibition, prothrombinase inhibition, prothrombin time (PT) an d activated partial thromboplastin time. Fifteen SD rats were divided into three groups；intact control group (or ally administrated with distilled water 5ml/kg) and two experimental group treated with extract of diospyros kaki calyx (EKC). Experimental rats were orally 600 mg/kg concentration of EKC and 200 mg/kg concentration of EKC. After an hour from administration, we anesthetized rats and made arteriovenous (AV) shunt rat models to study weight of thrombus, took whole blood to study content of thromboxane B2 and blood clotting time.Results：In vitro, EKC significantly increased inhibitory activity of FXa, prothrombinase compared with intact control group (*P<0.05). PT and aPTT were increased in EKC trea ted (600 mg/kg) group compared with intact control group (*P<0.05). In vivo, blood clotting time of experiment group treated with EKC 600 mg/kg were significantly increased compare with that of intact control group (p<0.05) and content of thromboxane B2 was significantly decreased in group treated with EKC 600 mg/kg in serum. The weight of thrombus were significantly reduced in group treated with EKC 600 mg/kg compa red with intact control group (p<0.05). But in vivo experiment study, those parameters of group treated with EKC 200 mg/kg were relatively decreased compared with those of intact control group without statistical significance.Conclusions：EKC has an antithrombic activity because of inhibition internal course such as FXa and prothrombin. And EKC inhibited a hole blood clotting in vivo experiment by low content of thromboxane B2.Key words：Diospyros Kaki Calyx, antithromboic activity, factor Xa assay, prothrombin time assay, thromboxane B2, arteriovenous shunt modle

Antibacterial And Antithrombic Activities Of Agrowastes Culture Extract Of P.Chrysogenum

Penicillium chrysogenum is a microfungus with a potent antibiotic production activity. It is also well known for its agrowastes biodegradation and enzyme production. This study investigated the use of agro waste based culture extract of a novel P. chrysogenum PCL 501 in antibacterial and antithrombic activities (thrombin, a serine protease is involved in blood clotting). The fungus was cultivated for a period of 240 h on cassava shavings and sugar cane pulp media in submerged fermentation and the culture extract was analyzed for its antibacterial and antithrombic activities, using benzyl penicillin as reference drug. The results revealed that the two agrowastes were well utilized by the fungus for growth and the culture extract had a potent antibacterial activity against E.coli and B.subtilis. Extract from cassava shavings show potency indices of 11.76 and 10.432 against E.coli and B.subtilis respectively and that from sugarcane pulps 17.95 and 11.41 against E.coli and B.subtilis respectively. The extract inhibited thrombin (serine protease) action which explains its antithrombic activities observed in terms of delayed clotting time. A similar pattern of inhibition was also observed with the reference drug (Benzyl penicillin).

We-P11:207 Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs

We-P11:207 Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs

Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs

The anti-thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW), which is consisted of 11 herbs (indicated as concentrations) of Rehmanniae radix 24%, Hominis placenta 5%, Testudinis carapax 9%, Eucommiae cortex 9%, Asparagi radix 9%, Phellodendri cortex 9%, Achyranthis radix 7%, Liriopis tuber 7%, Angelicae sinensis radix 7%, Ginseng radix 6%, and Schizandrae fructus 3%, were investigated. The extracts of DJW and its 11 herbs, except G. radix, A. sinensis radix and S. Fructus, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. Also the extract inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In in vitro experiments, the extract was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. In conclusion, the protection of extracts of Korean herbs on the ischemic infarction induced artificially might be related to their inhibitory effects on DIC, platelet coagulation and thrombic action.

The Neuroprotective Effects of BNG-1: A New Formulation of Traditional Chinese Medicines for Stroke

BNG-1, a novel mixture of traditional Chinese medicines with a long history in the treatment of stroke, exhibited acute neuroprotection effect on rats with middle cerebral artery occlusion (MCAO). Anti-ischemic effects were seen in both animals receiving BNG-1 before the ischemic insult as well as in animals receiving the drug formulation after surgical occlusion of the artery. Anti-thrombic activity was seen in vitro to inhibit arachidonic acid-induced platelet aggregation and in vivo to prolong bleeding time in mice. BNG-1 was also found to inhibit several phosphodiesterase (PDE) isoforms with potency order of the following rank: PDE 1 > PDE 3 > PDE 6 > PDE 2 > PDE 4 > PDE 5. Other pre-clinical results and emerging clinical data coupled with the present findings suggest that BNG-1 may be a safe and effective therapy for both the prevention and treatment of cerebral stroke. Moreover, the fundamental cellular mechanism underlying its therapeutic effects may result from phosphodiesterase inhibition.

Novel polysaccharide-decorated poly(isobutyl cyanoacrylate) nanoparticles.

The aim of this work was to synthesize new surface-modified nanoparticles using a radical emulsion polymerization of an alkyl cyanoacrylate. Isobutyl cyanoacrylate was polymerized in nitric acid 0.2 M containing a polysaccharide (0.1375 g) and cerium (8 x 10(-2) M). After 1 h, the pH was adjusted to 7.0, and the nanoparticles were purified by dialysis. Nanoparticle characterization included scanning electron microscopy, quasi-elastic light scattering, zeta potential determination, measurements of the complement activation induced by different polysaccharide-coated nanoparticles and of the antithrombic activity of heparin. Dispersions of spherical particles were obtained using various polysaccharides. The particle diameter varied from 90 nm to several micrometers, and the zeta potential depended on the molecular weight and the nature and charge of the polysaccharide. Surface analysis performed by ESCA confirmed the presence of polysaccharides at the nanoparticle surface. The nanoparticles were very stable, and the biologic activity of the polysaccharide was preserved. Complement activation was influenced by the polysaccharide characteristics. A new method based on radical emulsion polymerization of isobutyl cyanoacrylate initiated by polysaccharides and cerium was developed to prepare nanoparticles. It leads, in a single step, to nanoparticles with surface properties defined by the polysaccharide. This method is a new concept for the development of biomimetic drug carriers with multiple functions.

Syntheses of cyclic prodrugs of RGD peptidomimetics with various macrocyclic ring sizes: evaluation of physicochemical, transport and antithrombic properties.

The objective of this work was to synthesize cyclic prodrugs 1a-d of RGD peptidomimetics 2a-d with various ring sizes (n[CH2] = 1, 3, 5 and 7) and to evaluate the effect of ring size on their transport, physicochemical, enzymatic stability, and antithrombic properties. The syntheses of cyclic prodrugs 1a-d were achieved by converging two key intermediates, Boc-Phe-O-CH2-OCO-OpNP (5) and H2N-(CH2)n-CO-Asp(OBzl)-OTce (8a-d), to give linear precursors Boc-Phe-O-CH2-OCO-HN-(CH2)n-CO-Asp(OBzl)-OTce (9a-d). The N- and C-terminus protecting groups were removed from 9a-d to give 10a-d. Linear precursors 10a-d were cyclized, and the remaining Bzl-protecting group was removed to produce cyclic prodrugs 1a-d in around 20% overall yield. The linear RGD peptidomimetics (2a-d) were synthesized using standard Boc-amino acid chemistry by solution-phase method. Increasing the ring size by adding methylene groups also increases the hydrophobicity of the cyclic prodrugs and parent RGD peptidomimetics. The transport properties of cyclic prodrugs 1c and 1d were 2.6- and 4.4-fold better than those of parent compounds 2c and 2d, respectively. These results suggest that increasing the hydrophobicity of the cyclic prodrugs and parent RGD peptidomimetics enhanced their transport properties. The hydrodynamic radii of the cyclic prodrugs were also smaller than those of their respective parent compounds, suggesting that the change in size may contribute to their transport properties. The chemical stability of the cyclic prodrugs was affected by the ring size, and the cyclic prodrug with the larger ring size (i.e. 1d) was more stable than the smaller one (i.e. 1a). All the cyclic prodrugs were more stable at pH 4 than at pH 7 and 10. Prodrug-to-drug conversion could be induced by isolated esterase as well as esterase found in human plasma. An increase in the length of methylene group (n[CH2] = 1, 3, 5, 7) enhanced the antithrombic activity of the prodrugs and the parent compounds. In summary, the ring size of cyclic prodrugs affected their transport, physicochemical, and antithrombic properties.

Synthesis and comparison of physicochemical, transport, and antithrombic properties of a cyclic prodrug and the parent RGD peptidomimetic

Cyclic prodrug 1 was derived from RGD peptidomimetic 2 by linking the amino and carboxylic acid groups via an (acyloxy)alkoxy linker. The formation of a cyclic prodrug can transiently alter the physicochemical properties of the RGD peptidomimetic. Cyclic prodrug 1 was synthesized via the key intermediate 8 , and the synthesis of this key intermediate was accomplished using two different routes. Cyclic prodrug 1 has a smaller hydrodynamic radius and higher membrane interaction potential than those of the parent RGD peptidomimetic 2 . The cell membrane permeation of cyclic prodrug 1 is twice that of the parent peptidomimetic 2 . The prodrug-to-drug conversion can be carried out in isolated porcine esterase as well as human plasma. The cyclic prodrug is more stable at pH 4 than pH 7, and is very unstable at pH 10. The cyclic prodrug has antithrombic activity, suggesting that it can be converted to the RGD peptidomimetic in platelet-rich plasma (PRP).

Synthesis of a novel cyclic prodrug of RGD peptidomimetic to improve its cell membrane permeation

The objective of this work was to synthesize cyclic prodrug 2 derived from the parent RGD peptidomimetic 1 and to evaluate its chemical and enzymatic stabilities and antithrombic activity. Cyclic prodrug 2 was formed to improve the cell membrane permeation of RGD peptidomimetic 1 by transiently masking the unfavorable physicochemical properties of compound 1. Cyclic prodrug 2 was synthesized by linking the amino and carboxylic acid groups of parent 1 via the (acyloxy)alkoxy promoiety. The prodrug-to-drug conversion of cyclic prodrug 2 was evaluated in isolated esterase and human plasma in the absence and presence of the esterase inhibitor paraoxon. The rate of hydrolysis of cyclic prodrug 2 was significantly faster in plasma ( t 1/2=33.5±0.6 min) than in PBS ( t 1/2=314±11 min). Cyclic prodrug 2 was converted by esterase to the parent compound 1 and this conversion was inhibited by an esterase inhibitor, paraoxon. The IC 50 (4 μM) of cyclic prodrug 2 was higher than the IC 50 (1.9 μM) of parent drug 1. The antithrombic activity of cyclic prodrug 2 depends on the incubation time in platelet-rich plasma; the activity increases with incubation time, suggesting that the prodrug-to-drug conversion is time-dependent and mediated by esterase. Cyclic prodrug 2 was more stable under acidic and neutral conditions than under basic conditions, suggesting that handling and formulation of this prodrug should be undertaken under acidic conditions.

Synthesis and QSAR Studies in 2-( N-aryl- N-aroyl)amino-4,5-dihydrothiazole Derivatives as Potential Antithrombotic Agents

A series of 2-( N-aryl- N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure–Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best ( r>0.8) with electronic parameters ( F , σ or μ) having high statistical significance >99.9% (F 2,22>15.0; F 2,22α:0.001=11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.

Preparation and characterization of nanoparticles bearing heparin or dextran covalently-linked to poly(methyl methacrylate)

Nanoparticles have been obtained directly in aqueous media, from amphiphilic copolymers synthesized by radical polymerization of methyl methacrylate (MMA) initiated by Ce(IV) ions in the presence of heparin or dextran. The reaction conditions under which the copolymers spontaneously formed nanoparticles depended on the type of polysaccharide and on the concentrations of the reagents. Fluorescent nanoparticles containing N-vinyl carbazole (NVC), covalently linked to PMMA, were also prepared by random copolymerization of MMA and NVC in similar polymerization systems. The non-fluorescent nanoparticle suspensions were stable for several months without using surfactant. The fluorescent particles were larger and less stable then the unlabelled ones. Since all the particles are monodisperse, and in the submicron range, they can be used as models of drug carriers; the covalently-linked fluorescent species allowing them to be followed in vivo. The average molecular weights of the PMMA blocks of the copolymers and of oxidized heparin and dextran were determined by viscometry and/or gel permeation chromatography. The antithrombic activity of oxidized heparin was measured. The results show that the polysaccharide chains were cleaved by Ce(IV) in aqueous nitric acid, resulting in formation of block copolymers made of one or two blocks of PMMA linked to the ends of one polysaccharide block. Taken together, the results suggest that the particles were organized with the polysaccharidic moieties on the surface of the particles and the more hydrophobic PMMA or P(MMA-co-NVC) in the core, in a brush-like structure. This should confer 'stealth' properties to such particles.