S. Maltinti

Effect of chitosan and dextran on the properties of poly(vinyl alcohol) hydrogels

Hydrogels are three-dimensional polymeric networks very similar to biological tissues and potentially useful as drug delivery systems. Poly(vinyl alcohol)-based hydrogels containing different amounts of dextran or chitosan were prepared using the freezing–thawing method. Repeated freezing–thawing cycles of a poly(vinyl alcohol) (PVA) aqueous solution lead to the formation of crystallites which act as cross-linking sites, and a hydrogel with a high capacity to swell is obtained. The effects of the two different polysaccharides on the properties of the obtained materials were investigated by differential scanning calorimetry, dynamic mechanical analysis and scanning electron microscopy. In addition the release with time of poly(vinyl alcohol) in aqueous medium, was monitored and evaluated. On the basis of the obtained results it seems that the presence of dextran favors the crystallization process of PVA, allowing the formation of a more ordered and homogeneous structure. Instead, chitosan seems to perturb the formation of PVA crystallites leading to a material with a less regular structure.

Accuracy of b-GGT fraction for the diagnosis of non-alcoholic fatty liver disease

Serum gamma‐glutamyltransferase (GGT) activity is a sensitive but non‐specific marker of non‐alcoholic fatty liver disease (NAFLD). Recently, four GGT fractions (big‐, medium‐, small‐, free‐GGT) were described in humans.

New composites of hydroxyapatite and bioresorbable macromolecular material.

Composite materials were prepared by mixing in different proportions of hydroxyapatite (HA) and poly(ε-caprolactone-oxyethylene-ε-caprolactone) block copolymer (PCL-POE-PCL) to produce a new resorbable material for biomedical applications. This material has proved to be very interesting for production of periodontal membranes. Mechanical properties are linearly proportional to the amount of HA introduced. Fourier transform infrared (FTIR) investigations have pointed out that HA is able to influence some close ε-caprolactone molecules to start its homopolymerization giving PCL with an end chain ionic bonding. HA grains are therefore surrounded by a film of PCL which grants close connection of HA grains within copolymeric matrix. This interface bond with PCL is, however, an interesting occurrence for preparations of HA/PCL composites. ©1999 Kluwer Academic Publishers

Hydrogels based on chitosan and dextran as potential drug delivery systems.

The release of human growth hormone (GH) from bioartificial polymeric materials in the form of hydrogels, was measured in vitro for up to 3 weeks. Poly(vinyl-alcohol) (PVA) was blended, in different ratios, with two biological polymers, dextran and chitosan respectively. These blends were used to prepare hydrogels, using a freeze–thawing method. The hydrogels were loaded with GH, and their potential use as delivery systems was investigated. The release with time of PVA, in aqueous medium, was also monitored and evaluated. Scanning electron microscopy was used to investigate the structure of the hydrogels. The results obtained indicated that GH can be released from both dextran/PVA and chitosan/PVA hydrogels. The initial GH concentration used for sample loading affected the total quantity of GH released but not the pattern of release. The amount of GH released was affected by the content of the biological component. The percentage of PVA released was low but it was, however, related to the content of chitosan and dextran in the blends. ©1999 Kluwer Academic Publishers

Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett's oesophagus for 1 year

Aliment Pharmacol Ther 2011; 33: 1019–1027

Release of 5-fluorouracil by biodegradable poly(ester-ether-ester)s. Part I: release by fused thin sheets

The 5-fluorouracil release by biodegradable ɛ-caprolactone and L-lactide copoly(ester-ether-ester)s was tested. The drug-copolymer mixture was formed by fusion in thin sheets, which were dipped in Dulbeccos PBS for time intervals ranging from one hour to two months. Each experiment shows a fast initial release, which subsequently slows down and stops at a limiting value, depending on the copolymer composition. This behavior was attributed to an extraction of the drug present on the sheet surface, due only to its shape, and to hydrogen bonds between the drug and the copolymers. The results obtained lead to a possibility of using such copolymers as “time-delayed” drug-releasing systems, when formed in specimens with smaller surface-to-volume ratio, which could minimize the fast initial extraction.

Fibers by bioresorbable poly(ester-ether-ester)s as potential suture threads: a preliminary investigation

Fibers made by a bioresorbable poly(ε-caprolactone)-block-poly(oxyethylene)-block-poly(ε-caprolactone) copolymer, having a number average molecular mass of about 200 000 Da and an average molar composition of 66% oxycaproyl units and 34% oxyethylene units, were melt-spun, with the aim at using them as suture threads. Their properties were investigated by the stress-strain test and by differential scanning calorimetry (DSC). The results obtained show that the properties of this material depend very strongly on the alignment of its macromolecules. In particular, the only partial alignment, obtainable by a relatively moderate drawing just after the extrusion, leads to values of elongation at break too high for use of the fibers as suture threads. The DSC analysis reveals interesting properties of the material, but also confirms their strong dependence on the extrusion procedure and on the mechanical treatment. In conclusion, the results of this preliminary study show that the spinning technique must be improved, and that further investigations are necessary to ascertain the possibility of using these poly(ester-ether-ester)s for the fabrication of suture threads.

Plasma gamma‐glutamyltransferase (GGT) activity in inflammatory bowel disease: Is the clinical laboratory plasma GGT assay sensitive enough for gastroenterology?

To the Editor: A recent study reports the association between polymorphisms of genes regulating plasma gamma-glutamyltransferase (GGT) activity and the risk of diabetes, cardiovascular, and other diseases, including inflammatory bowel disease (IBD). As remarked by the authors, the function of GGT is to make cysteine available for the synthesis of intracellular glutathione, thus a decrease in GGT gene expression may lead to decreased glutathione availability and may impair the efficiency of antioxidant defenses; this interpretation is in contrast with the fact that, in the case of diabetes and coronary atherosclerosis, the diseases are associated with increased values of plasma GGT rather than decreased values, and no disease has yet been associated with decreased levels of plasma GGT. In IBD a decrease in GGT activity in the inflamed intestinal mucosa has been reported, but a correlation between plasma GGT levels and IBD has never been found. To check whether this might depend on the modest sensitivity and reproducibility of the current clinical assay for GGT, we analyzed plasma samples from a small cohort of 48 subjects with IBD (27 Crohn’s disease and 21 ulcerative colitis) and 48 healthy subjects, matched for age and gender (Table 1). When the samples were assayed by the current routine clinical laboratory procedure, based on the hydrolysis of the chromogen gammaglutamyl-3-carboxy-4-nitroanilide, we did not find any difference between IBD patients and controls. We then repeated the analysis with a high sensitivity fluorescent assay, which allows the separate determination of the four GGT fractions present in human blood: b-GGT (molecular weight [MW] 2000 kDa), m-GGT, (MW 1000 kDa), s-GGT (MW 140 kDa), and f-GGT (MW 70 kDa). By this method we found that two of the four fractions, m-GGT and f-GGT, were significantly reduced in IBD as compared with controls (Table 1). Within the group with IBD, no correlation emerged by Pearson’s correlation analysis between the values of these fractions and the levels of fecal calprotectin, C-reactive protein, erythrocyte sedimentation rate, or therapy, thus suggesting that reduced mGGT and f-GGT are a trait of the disease, and not a consequence of its clinical activity. To our knowledge, this is the first report concerning the association between low plasma GGT activity and IBD, confirming the results of the study by Middelberg et al, and the first associating a human disease with decreased values of GGT, rather than increased values. The low sensitivity of the routine clinical assay for GGT seems to impair its diagnostic value and needs to be overcome, possibly opening new perspectives for the study of the many diseases associated with polymorphisms regulating GGT expression, and IBD in particular.

Composites Between Alumina and an Ester‐Ether‐Ester Bioresorbable Copolymer

Composites between alumina and the biore-sorbable (poly(e-caprolactone)-block-poly(oxyethylene)-block-poly(e-caprolactone) copolymer were obtained by reacting e-caprolactone with preformed poly(ethylene glycol), in the presence of ceramic alumina powder, at 185°C under vacuum. The mechanical properties, tested by compression and flexural strengths and Youngs modulus, show that the copolymer interacts poorly with the alumina grains. Both scanning electron and atomic force microscopy show a scare wettability between alumina and copolymer, as well as the aggregation of alumina micro-particles into clusters of big size. Both mechanical and morphological tests seem to indicate a stronger interaction between the alumina micro-particles than between the alumina surface and the reaction mixture during the polymerization, as well as a compacting effet by alumina on the forming copolymer. The FT-IR spectra of the composites show both copolymer and alumina absorption bands. The FT-IR analysis on the fractions of an extraction which CHCl 3 indicates the presence of traces of poly(e-caprolactone), stably linked to alumina. The polymerization of e-caprolactone with alumina alone in the same conditions gives poly(e-caprolactone), mainly free and in minor part linked to the alumina surface. Two polymerization mechanisms, simultaneously occuring, are proposed. The most relevant result of this work is the lack of chemical inertness of alumina towards e-caprolactone, which leads to reconsider also the use of alumina as a biochemically inert material.

Poly(allylammonium acrylate) as a drug-releasing matrix : II. Release of drugs entrapped into the polysalt structure

SummaryThe release of drugs, entrapped into the poly(allylammonium acrylate) (PAAC) polyelectrolyte complex structure, was tested for vitamin B12 (VitB12) and tetracycline (TCY). The PAAC-drug “composites” were obtained by synthesizing PAAC in the presence of either VitB12 or TCY. Weighed samples of the “composites” were sintered as tablets, which were dipped into Dulbecco’s PBS (pH 7.3); the release was followed spectrophotometrically. The tests show very low limiting release values, with different kinetic behaviours for TCY and VitB12. The results are discussed and attributed to strong ionic interactions between the polyelectrolyte complex and the dipolar ions VitB12 and TCY.