New multifunctional textile biomaterials for the treatment of leg venous insufficiency.

Acryloyl monomers have been synthesized by reaction of beta-cyclodextrin and troxerutin with acryloyl chloride and grafted on a knitted material obtained from polyamide 6.6 and polyurethane fibers. Polyamide grafted with beta-cyclodextrin derivative binds troxerutin as a physical complex. The obtained biomaterials have been tested in vivo on rats for their ability to deliver troxerutin (a flebotonic drug) to different skin areas (epidermis, dermis and vascular wall). The results showed that the new synthesized materials can act as multifunctional bioactive textiles that can display both compression (given by the textile material) and sustained venotonic and haemostatic properties (given by the troxerutin delivered from biomaterial to the skin).

Associative pullulan gels and their interaction with biological active substances.

This paper studies the synthesis and properties of anionic and/or amphiphilic pullulan microparticles crosslinked with epichlorohydrine or with sodium trimethaphosphate. The polysaccharide gels were physicochemically characterized and their interaction with enzymes (lysozyme) was studied with the aim to appreciate the performances for separation/purification/immobilization of the enzymes or controlled release drug systems.

Acrylic microspheres for oral controlled release of the biguanide buformin.

Spherical microparticles based on methacrylic acid-methyl methacrylate copolymer have been developed. The method chosen for the preparation of such microparticles was suspension radical copolymerization of acrylic comonomers in the presence of the ethyleneglycol dimethacrylate as crosslinking agent. The microparticles obtained were characterised by inverse size exclusion chromatography, scanning electron microscopy, swelling degree and exchange capacity. The porous volume of the microspheres ranged from 0.086 ml/g for the microparticles produced by a methacrylic acid/methyl methacrylate ratio of 1/3 and a 10% degree of crosslinking, to 8.57 ml/g for the microparticles produced by a methacrylic acid/methyl methacrylate ratio of 3/1 and 2% degree of crosslinking (in 0.1 N NaCl in phosphate buffer pH 7.4). Also the pore diameter of the swollen microparticles ranged from a few to 120 A. Buformin tosylate - a classical hypoglycaemic drug - was included in the polymer network of the microparticles during the polymerization process. Due to the water solubility of the drug and its low solubility in the organic phase, the entrapment yield did not exceed 15%. However the amount of encapsulated drug as well as the drug released from the microparticles, was dependent on the methacrylic acid/methyl methacrylate ratio, the degree of crosslinking and solvent/comonomers ratio.

Associative behaviour of hydrophobically modified carboxymethylpullulan derivatives.

Hydrophobically modified carboxymethylpullulan (HMCMP) samples were obtained by reaction of small amounts of C16 alkylamine on carboxylic groups of the corresponding polyacid. The molar contents of alkyl chains ranged from 1.3 to 6.8% with respect to the anhydroglucose units (AGU) and the degree of substitution (DS) of carboxylic groups varied from 0.76 to 0.84. Solution properties of the sodium salt of HMCMPs were studied mainly by viscometric and size-exclusion chromatography/light-scattering methods. The low-shear viscosity of modified pullulans in 0.1 M NaCl solutions drastically increases with the hydrophobic content and polymer concentrations and the 6.8% modified sample has a quite pseudoplastic behaviour. These data showed that the polymers aggregated intermolecularly and displayed a compact globular structure in dilute solution. Furthermore, addition of NaCl or ethanol induced a decrease in viscosity although the molecular weights remained approximately constant. These results are consistent with a collapse of the polysaccharide aggregates.

Preparation and characterization of anionic pullulan thermoassociative nanoparticles for drug delivery.

Thermoassociative nanoparticles were obtained through the crosslinking reaction of periodate oxidized carboxymethyl pullulan with two difunctional Jeffamines: ED-600 and ED-2003. The nanoparticles were characterized through (1)H NMR spectra; their particle size, determined by dynamic light scattering (DLS) presented a bimodal distribution, with dimensions varying as a function of amount and type of crosslinking agent used; transmission electron microscopy photos confirmed the spherical shape of the nanoparticles and their dimensions determined by DLS. Their amphiphilic character was evidenced by retention of the dyes: hydrophobic (Rose Bengal), amphiphilic (Brilliant Blue) and hydrophilic (Vitamin B12). The thermosensitive properties, more pronounced for ED-2003 crosslinked nanoparticles, were evidenced through absorbance variation, fluorescence and DLS measurements as a temperature function. The nanoparticles retain important amounts of anionic (diclofenac: 40-80 mg/g), cationic (methylene blue: 70-125 mg/g) and hydrophobic (alpha-tocopherol: 220-350 mg/g) drugs. The in vitro characterization of the drug-polymer conjugates recommends the synthesized nanoparticles as supports for drug delivery.

Bioactive cotton fabrics containing chitosan and biologically active substances extracted from plants.

The paper studies the obtaining of bioactive textiles using chitosan-coated fabrics, in which biologically active substances contained by Viola Tricolor (VT) - an extract of three Viola species (Violaceae) - were immobilized. Chitosan was applied on cotton fabric or on chemically modified cotton (having reactive -CHO or carboxymethyl groups), as tripolyphosphate (TPP) crosslinked fine particles, or by use of glutaraldehyde crosslinking agent. The amount of VT retained on the fabrics was found to depend on the procedure of chitosan application on the cotton. The obtained bioactive textiles are expected to have antioxidant activity due to the biologically active substances from VT; they can be used for obtaining clothes for people with allergies or other skin problems, assuring a controlled release of biomolecules. The study focuses on the in vitro release of VT retained on the fabrics, as well as on its antioxidant activity.

Effect of chitosan coating on the swelling and controlled release of a poorly water-soluble drug from an amphiphilic and pH-sensitive hydrogel.

In the present work, a new particulate controlled release system was prepared, by coating alginate-g-PCL/Ca(2+) beads with chitosan. The swelling behaviour and controlled release of a poorly water-soluble drug (theophylline) model were studied in media of varying pH, by simulating human fluids at 37 degrees C. In a simulated gastric fluid (SGF, pH 1.2), coated beads presented weak swelling (8-22%) and weak release rates (24-32% within 120min), and were able to protect the drug from this harsh environment. In a simulated intestinal fluid (SIF, pH 6.8), the swelling rates of amphiphilic beads (before disintegration) were strongly reduced (300-1100%) comparatively with those of uncoated beads (700-1700%). This can be explained by the strong electrostatic interactions between the amino groups of chitosan and the carboxylate groups of alginate-g-PCL, leading to the formation of a protective membrane of strong polyelectrolyte complex around the beads. This outermost layer effectively promoted the stability of beads under gastro-intestinal tract conditions, while the hydrophobic interactions between theophylline and PCL grafts allowed a considerable slowing down of the drug release. It was found out that combination of the protective effect of the polyelectrolyte membrane in SIF associated with the hydrophobicity of PCL grafts allowed to release a poorly water-soluble drug, in a controlled manner, for 7h, along a simulated gastro-intestinal tract.

New amphiphilic and pH-sensitive hydrogel for controlled release of a model poorly water-soluble drug.

This paper presents the development of new pH-sensitive, amphiphilic and biocompatible hydrogels based on alginate-g-PCL, cross-linked with calcium ions to form beads, prepared for controlled delivery of poorly water-soluble drug. We have focused our study on the effect of the length of PCL chains (530 and 1250 g mol(-1)). Swelling profiles obtained clearly indicated that these hydrogels swell slightly (10-14%) in a simulated gastric fluid (pH 1.2), and strongly (700-1300% before disintegration) in a simulated intestinal fluid (pH 6.8). In both media, rates of swelling were lower for beads based on amphiphilic derivatives than for alginate/Ca2+ ones due to the hydrophobic PCL grafts, and decreased when hydrophobic character increased. A model drug, theophylline, was entrapped into these hydrogels and release studies were carried out. The drug was protected in acidic fluid (only 14-20% of release for alginate-g-PCL hydrogel against 35% of release for alginate hydrogel during 350 min). The drug is released completely in neutral fluid due to ion exchanges and disintegration of the hydrogel. PCL leads to decrease in the release kinetics in SIF (2h for alginate-g-PCL/Ca2+ beads against 1h for alginate/Ca2+ beads). It was demonstrated that the establishment of clusters inside beads by intramolecular interactions between PCL grafts of 530 g mol(-1) in salt media allowed to retain the drug and to slow down its release considerably.

Aminated polysaccharides as bile acid sorbents: in vitro study.

Dextran, pullulan, and microcrystalline cellulose were cross-linked with 1-chloro-2,3-epoxypropane and reacted with N-(1-chloroethyl)-N,N-diethylamine or N-glycidyl-N,N,N-trialkylammonium chloride in order to obtain sorbents containing tertiary amino and/or quaternary ammonium groups. In vitro equilibrium sorption of cholic acid on these sorbents was studied in comparison with Cholestyramine, and in vitro dissociation of ionic complexes of cholic acid-sorbents was determined under dynamic conditions. The sorption capacity and the affinity of these sorbents for cholic acid were investigated in relation to the nature of the polymeric support, the swelling porosity of sorbent, the basicity of amino groups, and the nature of the substituents at the nitrogen atom. The maximum sorption capacity increases with the increase in amino group content, their basicity, and the length of alkyl substituents at the nitrogen atom. The affinity for cholic acid of all polysaccharide-based sorbents is higher than that of Cholestyramine. Dextran-based sorbents display the highest sorption affinity. It was found that there exists an optimum swelling porosity for the polysaccharide sorbents to attain the highest affinity for cholic acid. The dissociation rate of ionic complexes depends also on the nature of the polysaccharide and the swelling porosity and its lower for sorbents with higher sorption affinity.

Prolonged gastroprotective activity of a ranitidine-dextran conjugate.

The paper presents the influence of the ranitidine-dextran conjugate on the gastric secretion stimulated with carbachol on rats with a ligated pylorus [correction of ligaturated pilor]. The gastric lesions, the gastric juice volume and the total acidity at 6, 24 and 48 hours after the treatment were examined. Ranitidine serum content was determined by HPLC. Administration of the ranitidine-dextran conjugate produces a higher inhibition of gastric lesions at 48 hours than the administration of the free drug (61.4% versus 33.9%) and a prolonged action for more 48 hours. Synthesis of a macromolecular prodrug of ranitidine and its in vitro behavior was reported in a previous paper (11). The present paper studies the performances obtained in gastro-protective action by using the new ranitidine-dextran conjugate reported (11).

Hypolipidemic effect of a prodrug containing nicotinic acid in rats. Correlation with plasmatic levels.

We have studied a macromolecular prodrug that contains nicotinic acid bound on a polymeric support of dextran. We have determined plasmatic levels of nicotinic acid, by a HPLC method, after macromolecular conjugate administration for a 24 hours period. In order to study the hypolipidemic effect, triglyceride levels were determined and correlated with plasmatic levels of nicotinic acid. The obtained data show that, starting from 6 hours after polymeric conjugate administration, plasmatic levels of nicotinic acid are high enough to determine a significantly decrease in triglycerides level. As a conclusion we assume that the active substance was gradually released from the polymeric support leading to a prolonged presence of the active substance in the body, which caused a lowered triglycerides level.

Drug-induced immunodeficiency associated with nodal Kaposi's sarcoma.

A 40-year-old male showed a syndrome of acquired immunodeficiency after a prolonged use of antidiabetic sulfamides. The lesions were revealed by the biopsic examination of inguinal lymph nodes. Immunodeficiencies are usually associated with malignant lymphoma: our case was, however, associated with Kaposi's sarcoma.