Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar,Mohali, Punjab-160 062, India, Institute of Biochemistry, Faculty of Medicine, Polytechnic University, Via Ranieri 67, IT-60100 Ancona, Italy,Green Biotechnology Research Group, The Special Division for Human Life Technology, National Institute of Advanced Industrial Science andTechnology, 1-8-31 Midorigaoka, Ikeda, Osaka-563-8577, Japan, and Department of Medicinal Chemistry & Natural Products,The Hebrew University of Jerusalem, School of Pharmacy-Faculty of Medicine, Jerusalem 91120, IsraelReceived March 2, 2004

Chitosan chemistry and pharmaceutical perspectives.

Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical excipient. It is obtained by the partial deacetylation of chitin, the second most abundant natural polymer. Chitosan comprises a series of polymers varying in their degree of deacetylation, molecular weight, viscosity, pKa etc. The presence of a number of amino groups permit chitosan to chemically react with anionic systems, thereby resulting in alteration of physicochemical characteristics of such combinations. Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating and tablet coating properties. The polymer has also been investigated as a potential adjuvant for swellable controlled drug delivery systems. Use of chitosan in novel drug delivery as mucoadhesive, gene and peptide drug administration via the oral route as well as its absorption enhancing effects have been explored by a number of researchers. Chitosan exhibits myriad biological actions, namely hypocholesterolemic, antimicrobial and wound healing properties. Low toxicity coupled with wide applicability makes it a promising candidate not only for the purpose of drug delivery for a host of drug moieties (antiinflammatories, peptides etc.) but also as a biologically active agent. It is the endeavour of the present review to provide an insight into the biological and pharmaceutical profile of chitosan. Various investigations carried out recently are reported, although references to research performed on chitosan prior to the recent reviews have also been included, where appropriate.

https://onlinelibrary.wiley.com/doi/pdf/10.1211/0022357011776441

Chitosan: some pharmaceutical and biological aspects--an update.

: Background: Hemorrhage is a leading cause of death from trauma. An advanced hemostatic dressing could aug- ment available hemostatic methods. We studied the effects of a new chitosan dressing on blood loss, survival, and fluid use after severe hepatic injury in swine. Methods: Swine received chitosan dressings or gauze sponges. Standardized, severe liver injuries were induced. After 30 seconds, dressings were applied and resuscitation initiated. Blood loss, hemostasis, resuscitation volume, and 60- minute survival were quantified. Results: Posttreatment blood loss was reduced ( p less than 0.01) in the chitosan group (264 mL; 95% confidence interval [CI], 82 852 mL) compared with the gauze group (2,879 mL; 95% CI, 788 10,513 mL). Fluid use was reduced (p = 0.03) in the chitosan group (1,793 mL; 95% CI, 749 4,291) compared with the gauze group (6,614 mL; 95% CI, 2,519 17,363 mL). Survival was seven of eight and two of even in the chitosan and gauze groups ( p = 0.04), respectively. Hemostasis was improved in the chitosan group (p = 0.03). Conclusion: A chitosan dressing reduced hemorrhage and improved survival after severe liver injury in swine. Further studies are warranted.

/pdf/effect-of-a-chitosan-based-hemostatic-dressing-on-blood-loss-324bkyzn1v.pdf

Effect of a chitosan-based hemostatic dressing on blood loss and survival in a model of severe venous hemorrhage and hepatic injury in swine.

Microbial biofilm formed on abiotic surfaces is an important area of research because of the wide range of possible affects and the disinfectant resistance of the cells. The colonization of solid surfaces by microorganisms is a very complicated process that depends mostly on extracellular molecule production. The biosynthesis of EPS reflected not only the attachment and aggregation process but also provided an optimal environment for the exchange of genetic material between the cells. The comparative and comprehensive analysis of all documented data concerning EPS production can enable the development and effective con trol strategies for biofilms. In this review some of the basic concepts concerning the biosynthesis of EPS and potential function of these compounds in biofilm development were discussed. In the paper the positive and negative aspects of EPS production in the environment also were described.

Biosynthesis of Extracellular Polymeric Substances (EPS) and Its Role in Microbial Biofilm Formation

Biodegradability, biocompatibility and capacity to promote the synthesis of hyaluronan are main characteristics of chitin-derived wound healing materials, whose biological significance in the human body depends largely on the actions that certain hydrolases exert on them The resulting chitooligomers stimulate various cells, while the released monomers are phosphorylated and incorporated into hyaluronan, keratan sulphate and chondroitin sulphate, components of the intracellular matrix and connective tissue The healing process favoured by these materials is examined in terms of macrophage activation, cytokine production by macrophages and fibroblasts, antiinflammatory action, angiogenesis stimulation, granulation and scar formation Current biomedical applications are illustrated by the treatment of leg ulcers, the use of skin substitutes, and the regeneration of bone, nerve and meniscus tissues

Biochemistry, histology and clinical uses of chitins and chitosans in wound healing.

The effects of chitosan have been investigated on eighty patients with renal failure undergoing long-term stable haemodialysis treatment. The patients were tested after a control treatment period of 1 week. Half were fed 30 chitosan tablets (45 mg chitosan/tablet) three times a day. Ingestion of chitosan effectively reduced total serum cholesterol levels (from 10.14 +/- 4.40 to 5.82 +/- 2.19 mM) and increased serum haemoglobin levels (from 58.2 +/- 12.1 to 68 +/- 9.0 g L-1). Significant reductions in urea and creatinine levels in serum were observed after 4 weeks of chitosan ingestion. The feeling of physical strength, the appetite and the sleep of patients in the treatment group had improved significantly after 12 weeks of ingestion, compared with those of patients in the control group. During the treatment period, no clinically problematic symptoms were observed. These data suggest that chitosan might be effective treatment for renal failure patients, although the mechanism of the effect should be investigated further.

Effect of chitosan on renal function in patients with chronic renal failure

The glycoside composition and sequence of an extracellular polysaccharide flocculant of Klebsiella pneumoniae H12 was analyzed. GC and HPLC analysis of the acid-hydrolysate identified its constituent monosaccharides as D-Glc, D-Man, D-Gal, and D-GlcA in an approximate molar ratio of 3.9:1.0:2.3:3.6. To analyze the glycoside sequence, the polysaccharide was partially hydrolyzed by acid and enzyme treatment. GC, HPLC, TLC, MALDI-TOF/MS, and 1H- and 13C- NMR spectroscopy characterized the obtained oligosaccharides. The results clarified the partial structure of H12 polysaccharide as a linear polymer of a unit of pentasaccharide with a side chain of one D-GlcA to D-Glc moiety (see below). Although the existence of other sequences or other constituent glycosides could not be fully excluded, H12 polysaccharide must be a novel types as such a complicated unit for a polymer has not so far been reported. The partial structure of a H12 polysaccharide flocculant is also discussed in this report. [structure: see text]

Structural analysis of an extracellular polysaccharide bioflocculant of Klebsiella pneumoniae.

Because of the widespread use of aluminium- and calcium-containing phosphate binders for the control of hyperphosphataemia in patients with end-stage renal failure, an iron(III) chitosan complex was synthesised and fed to rats to measure its effect on serum phosphorus and calcium, intestinal phosphate binding and phosphate absorption. Thirty-six Wistar rats were randomly selected and distributed into a baseline group (n = 6), a control group (n = 8 (days 0-15), n = 8 (days 16-30)) and a treatment group (n = 8 (days 0-15), n = 8 (days 16-30)). The control groups ingested AIN-76 diet mix with a 1% w/w fibre content; however, the treatment groups had the fibre content completely substituted with iron(III) chitosan. The mean weights of the treated rats were slightly lower from 15 days (not significant); but overall, rat growth was not stunted in the treatment groups. The serum phosphorus levels of the treated group (n = 8) were significantly reduced after 15 days (P = 0.004; control: 5.7+/-0.9 mg dL(-1); treatment: 4.4+/-0.5 mg dL(-1); 95% CI of difference: 0.5-2.2) and 30 days (P = 0.002; control: 5.5+/-0.9 mg dL(-1); treatment = 4.1+/-06 mg dL(-1); 95% CI of difference: 0.6-2.3) as compared with the respective control group. The serum calcium-phosphorus product was 62.0+/-12.1 mg2 dL(-2) for the control and 45.1+/-6.6 mg2 dL(-2) for the treatment group after 30 days (P = 0.004). The serum iron concentration of the treatment group did not differ from the baseline value after 15 and 30 days, but the treatment group was significantly higher than the control group (P<0.05) after 30 days. The faeces phosphorus levels (mg day(-1)) were higher (P<0.01) and its iron content was much higher (P<0.01) for the treated group. The urine phosphorus (mg kg(-1)) was not significantly reduced for the treated group, but the mean was consistently less. The kidney and liver weights of both groups were similar, but the phosphorus content of the kidney (mg (g kidney)(-1)) was higher for the treated group after 30 days (P = 0.041; control, 4.2+/-1.2 mg g(-1) vs treatment, 5.6+/-1.4 mg g(-1). Because iron(III) chitosan had a high phosphorus-binding capacity of 308 (mg P) per gram of Fe3+ for both the in-vitro (pH 7.5) and in-vivo studies, which is greater than nearly all commonly used phosphate binders, and a small net phosphorus absorption difference of 3.7 mg day(-1), it is an efficient phosphate binder for lowering serum phosphate levels without increasing serum calcium levels.

Effect of iron(III) chitosan intake on the reduction of serum phosphorus in rats.

Methane was decomposed to hydrogen and carbon nanotubes (CNTs)
by microwave plasma, using Fe/Si catalyst activated by biased (—150
V) hydrogen plasma for various treatment times. Upon exposure to biased
hydrogen plasma, the catalyst surface becomes lumpy within 1 min, coheres
between 5 and 10 min and forms particles after 20 min. The methane conversion
increased up to 93% over the treatment time of 5 min. The hydrogen yield showed
as similar tendency as the methane conversion and kept 83% at treatment time of 5
min. The treatment time up to 1 min increased the amount of deposited carbon,
and after treatment time of 5 min it dropped; then again after treatment time
of 20 min, it increased to reach a maximum value of 22 gc/gcat.
Deposited carbon was found to be consisted of carbon nanotubes. It grew
vertically on the catalyst surface and reached a maximum length of 30.7 nm
after treatment time of 10 min. Multiple types of CNTs were present, and the CNT
diameters decreased with increasing plasma treatment time.

https://file.scirp.org/pdf/GSC_2013022613140901.pdf

Direct Preparation of Hydrogen and Carbon Nanotubes by Microwave Plasma Decomposition of Methane over Fe/Si Activated by Biased Hydrogen Plasma

The microwave induced argon plasma was applied to the preparation of NaOH-activated carbon from sugar cane bagasse. The distinguished feature of the heating technique with this cold plasma is the short operation time. The carbonization and the activation process were finalized in one step within 3 min. The prepared activated carbon with NaOH ratio 3 to bagasse characterized using N2 adsorption of type IV (IUPAC classification) to give specific surface area of 1980 m2/g and mesopore volume of 0.73 ml/g. It also showed a higher specific capacitance of 201 F/g in 1 M H2SO4 solution (with standard three electrodes) than the corresponding one by the conventional heating, previously reported. The other features were the absence of oxygen groups and the presence of carbon centered stable radicals, detected by ESR spectra, on the surface.

/pdf/short-time-preparation-of-naoh-activated-carbon-from-sugar-1i666gdrqw.pdf

Yasuyuki Takiguchi

Papers

Effect of chitosan on renal function in patients with chronic renal failure

Structural analysis of an extracellular polysaccharide bioflocculant of Klebsiella pneumoniae.

Effect of iron(III) chitosan intake on the reduction of serum phosphorus in rats.

Direct Preparation of Hydrogen and Carbon Nanotubes by Microwave Plasma Decomposition of Methane over Fe/Si Activated by Biased Hydrogen Plasma

Short-Time Preparation of NaOH-Activated Carbon from Sugar Cane Bagasse Using Microwave Plasma Heating