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Special Issue "Advances in Marine Chitin and Chitosan II, 2017"

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 January 2017)

Special Issue Editors

Guest Editor
Dr. Hitoshi Sashiwa

Kaneka Co., Ltd, 5-1-1 Torikai-Nishi, Settsu, Osaka 566-0072 Japan
Website | E-Mail
Phone: +81-72-653-8333
Interests: chemical modification of chitin and chitosan and their biomedical applications; Biodegradable Polymer; Bio-based polymer
Guest Editor
Prof. Dr. David Harding

Institute of Fundamental Sciences, Massey University, Private Bag 11 222, Palmerston North, 4442, New Zealand
Website | E-Mail
Phone: +6421767565
Interests: hydrogels and other biopolymers

Special Issue Information

Dear Colleagues,

As a result of our call in 2014 for submissions to a Special Issue, Advances in Marine Chitin and Chitosan in Marine Drugs, we are now pleased to tell you that this issue has been published. Twenty high class papers were included in this issue, which we now plan to publish as a book. In addition we now seek to publish a further Special Issue, Advances in Marine Chitin and Chitosan II, 2017, in Marine Drugs. As before, we plan to produce a strong, very exciting issue that will encompass breakthroughs in high value, scientific and industrial chitin and chitosan research. Despite significant advances in chitin and chitosan research since the 1970s, current overviews in recent publications involving chitin and chitosan research advances need reporting.

We look forward very much to your input.

Dr. Hitoshi Sashiwa,
Prof. Dr. David Harding,
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chitin
  • chitosan
  • chito-oligosaccharide
  • glucosamine
  • N-acetyl-D-glucosamine
  • chemical modification
  • controlled drug delivery
  • hydrogels
  • tissue engineering
  • nanomaterial

Related Special Issue

Published Papers (25 papers)

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Research

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Open AccessArticle Fluorescent Property of Chitosan Oligomer and Its Application as a Metal Ion Sensor
Mar. Drugs 2017, 15(4), 105; doi:10.3390/md15040105
Received: 26 December 2016 / Revised: 13 March 2017 / Accepted: 29 March 2017 / Published: 4 April 2017
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Abstract
An aqueous solution was successfully prepared using a low-molecular-weight chitosan oligomer and FITC, and its structural and fluorescent properties were observed by using 1H NMR, 13C NMR, FT-IR, XRD, UV-Vis, and PL spectrometry. Its application as a metal ion sensor was
[...] Read more.
An aqueous solution was successfully prepared using a low-molecular-weight chitosan oligomer and FITC, and its structural and fluorescent properties were observed by using 1H NMR, 13C NMR, FT-IR, XRD, UV-Vis, and PL spectrometry. Its application as a metal ion sensor was also evaluated. The fluorescence in the water-soluble chitosan oligomer was a result of the carbamato anion (NHCOO-), and a synthesized FITC-labeled chitosan oligomer exhibited an effective detection effect for copper ion as well as energy transfer by the ion near FITC that caused a fluorescence decrease (quenching). The chitosan oligomer was confirmed to be applicable as a selective and sensitive colorimetric sensor to detect Cu2+. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Chitin Oligosaccharide (COS) Reduces Antibiotics Dose and Prevents Antibiotics-Caused Side Effects in Adolescent Idiopathic Scoliosis (AIS) Patients with Spinal Fusion Surgery
Mar. Drugs 2017, 15(3), 70; doi:10.3390/md15030070
Received: 12 January 2017 / Revised: 19 February 2017 / Accepted: 8 March 2017 / Published: 14 March 2017
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Abstract
Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide
[...] Read more.
Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG (p < 0.05), respectively. COS reduces the side effects caused by antibiotics (p < 0.05). COS improved biochemical indexes and reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF) alpha. COS reduced the antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Chitosan-Based Nanomedicine to Fight Genital Candida Infections: Chitosomes
Mar. Drugs 2017, 15(3), 64; doi:10.3390/md15030064
Received: 27 January 2017 / Revised: 25 February 2017 / Accepted: 1 March 2017 / Published: 4 March 2017
Cited by 1 | PDF Full-text (1517 KB) | HTML Full-text | XML Full-text
Abstract
Vaginal infections are associated with high recurrence, which is often due to a lack of efficient treatment of complex vaginal infections comprised of several types of pathogens, especially fungi and bacteria. Chitosan, a mucoadhesive polymer with known antifungal effect, could offer a great
[...] Read more.
Vaginal infections are associated with high recurrence, which is often due to a lack of efficient treatment of complex vaginal infections comprised of several types of pathogens, especially fungi and bacteria. Chitosan, a mucoadhesive polymer with known antifungal effect, could offer a great improvement in vaginal therapy; the chitosan-based nanosystem could both provide antifungal effects and simultaneously deliver antibacterial drugs. We prepared chitosan-containing liposomes, chitosomes, where chitosan is both embedded in liposomes and surface-available as a coating layer. For antimicrobial activity, we entrapped metronidazole as a model drug. To prove that mucoadhesivness alone is not sufficient for successful delivery, we used Carbopol-containing liposomes as a control. All vesicles were characterized for their size, zeta potential, entrapment efficiency, and in vitro drug release. Chitosan-containing liposomes were able to assure the prolonged release of metronidazole. Their antifungal activity was evaluated in a C. albicans model; chitosan-containing liposomes exhibited a potent ability to inhibit the growth of C. albicans. The presence of chitosan was crucial for the system’s antifungal activity. The antifungal efficacy of chitosomes combined with antibacterial potential of the entrapped metronidazole could offer improved efficacy in the treatment of mixed/complex vaginal infections. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Determination of Inorganic Cations and Anions in Chitooligosaccharides by Ion Chromatography with Conductivity Detection
Mar. Drugs 2017, 15(2), 51; doi:10.3390/md15020051
Received: 8 January 2017 / Revised: 10 February 2017 / Accepted: 16 February 2017 / Published: 22 February 2017
Cited by 1 | PDF Full-text (732 KB) | HTML Full-text | XML Full-text
Abstract
Chitooligosaccharides (COSs) are a promising drug candidate and food ingredient because they are innately biocompatible, non-toxic, and non-allergenic to living tissues. Therefore, the impurities in COSs must be clearly elucidated and precisely determined. As for COSs, most analytical methods focus on the determination
[...] Read more.
Chitooligosaccharides (COSs) are a promising drug candidate and food ingredient because they are innately biocompatible, non-toxic, and non-allergenic to living tissues. Therefore, the impurities in COSs must be clearly elucidated and precisely determined. As for COSs, most analytical methods focus on the determination of the average degrees of polymerization (DPs) and deacetylation (DD), as well as separation and analysis of the single COSs with different DPs. However, little is known about the concentrations of inorganic cations and anions in COSs. In the present study, an efficient and sensitive ion chromatography coupled with conductivity detection (IC-CD) for the determination of inorganic cations Na+, NH4+, K+, Mg2+, Ca2+, and chloride, acetate and lactate anions was developed. Detection limits were 0.01–0.05 μM for cations and 0.5–0.6 μM for anions. The linear range was 0.001–0.8 mM. The optimized analysis was carried out on IonPac CS12A and IonPac AS12A analytical column for cations and anions, respectively, using isocratic elution with 20 mM methanesulfonic acid and 4 mM sodium hydroxide aqueous solution as the mobile phase at a 1.0 mL/min flow rate. Quality parameters, including precision and accuracy, were fully validated and found to be satisfactory. The fully validated IC-CD method was readily applied for the quantification of various cations and anions in commercial COS technical concentrate. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Influence of Chitosan Swelling Behaviour on Controlled Release of Tenofovir from Mucoadhesive Vaginal Systems for Prevention of Sexual Transmission of HIV
Mar. Drugs 2017, 15(2), 50; doi:10.3390/md15020050
Received: 30 September 2016 / Revised: 13 February 2017 / Accepted: 16 February 2017 / Published: 21 February 2017
Cited by 2 | PDF Full-text (2795 KB) | HTML Full-text | XML Full-text
Abstract
The main challenges facing efforts to prevent the transmission of human immunodeficiency virus (HIV) are the lack of access to sexual education services and sexual violence against young women and girls. Vaginal formulations for the prevention of sexually transmitted infections are currently gaining
[...] Read more.
The main challenges facing efforts to prevent the transmission of human immunodeficiency virus (HIV) are the lack of access to sexual education services and sexual violence against young women and girls. Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Vaginal mucoadhesive tablets can be developed by including natural polymers that have good binding capacity with mucosal tissues, such as chitosan or guar gum, semisynthetic polymers such as hydroxypropylmethyl cellulose, or synthetic polymers such as Eudragit® RS. This paper assesses the potential of chitosan for the development of sustained-release vaginal tablets of Tenofovir and compares it with different polymers. The parameters assessed were the permanence time of the bioadhesion—determined ex vivo using bovine vaginal mucosa as substrate—the drug release profiles from the formulation to the medium (simulated vaginal fluid), and swelling profiles in the same medium. Chitosan can be said to allow the manufacture of tablets that remain adhered to the vaginal mucosa and release the drug in a sustained way, with low toxicity and moderate swelling that ensures the comfort of the patient and may be useful for the prevention of sexual transmission of HIV. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Short-Chain Chitin Oligomers: Promoters of Plant Growth
Mar. Drugs 2017, 15(2), 40; doi:10.3390/md15020040
Received: 20 December 2016 / Revised: 16 January 2017 / Accepted: 6 February 2017 / Published: 15 February 2017
Cited by 1 | PDF Full-text (1910 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chitin is the second most abundant biopolymer in nature after cellulose, and it forms an integral part of insect exoskeletons, crustacean shells, krill and the cell walls of fungal spores, where it is present as a high-molecular-weight molecule. In this study, we showed
[...] Read more.
Chitin is the second most abundant biopolymer in nature after cellulose, and it forms an integral part of insect exoskeletons, crustacean shells, krill and the cell walls of fungal spores, where it is present as a high-molecular-weight molecule. In this study, we showed that a chitin oligosaccharide of lower molecular weight (tetramer) induced genes in Arabidopsis that are principally related to vegetative growth, development and carbon and nitrogen metabolism. Based on plant responses to this chitin tetramer, a low-molecular-weight chitin mix (CHL) enriched to 92% with dimers (2mer), trimers (3mer) and tetramers (4mer) was produced for potential use in biotechnological processes. Compared with untreated plants, CHL-treated plants had increased in vitro fresh weight (10%), radicle length (25%) and total carbon and nitrogen content (6% and 8%, respectively). Our data show that low-molecular-weight forms of chitin might play a role in nature as bio-stimulators of plant growth, and they are also a known direct source of carbon and nitrogen for soil biomass. The biochemical properties of the CHL mix might make it useful as a non-contaminating bio-stimulant of plant growth and a soil restorer for greenhouses and fields. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Chitosan Oligosaccharide Reduces Propofol Requirements and Propofol-Related Side Effects
Mar. Drugs 2016, 14(12), 234; doi:10.3390/md14120234
Received: 2 November 2016 / Revised: 24 November 2016 / Accepted: 29 November 2016 / Published: 21 December 2016
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Abstract
Propofol is one of the main sedatives but its negative side effects limit its clinical application. Chitosan oligosaccharide (COS), a kind of natural product with anti-pain and anti-inflammatory activities, may be a potential adjuvant to propofol use. A total of 94 patients receiving
[...] Read more.
Propofol is one of the main sedatives but its negative side effects limit its clinical application. Chitosan oligosaccharide (COS), a kind of natural product with anti-pain and anti-inflammatory activities, may be a potential adjuvant to propofol use. A total of 94 patients receiving surgeries were evenly and randomly assigned to two groups: 10 mg/kg COS oral administration and/or placebo oral administration before being injected with propofol. The target-controlled infusion of propofol was adjusted to maintain the values of the bispectral index at 50. All patients’ pain was evaluated on a four-point scale and side effects were investigated. To explore the molecular mechanism for the functions of COS in propofol use, a mouse pain model was established. The activities of Nav1.7 were analyzed in dorsal root ganglia (DRG) cells. The results showed that the patients receiving COS pretreatment were likely to require less propofol than the patients pretreated with placebo for maintaining an anesthetic situation (p < 0.05). The degrees of injection pain were lower in a COS-pretreated group than in a propofol-pretreated group. The side effects were also more reduced in a COS-treated group than in a placebo-pretreated group. COS reduced the activity of Nav1.7 and its inhibitory function was lost when Nav1.7 was silenced (p > 0.05). COS improved propofol performance by affecting Nav1.7 activity. Thus, COS is a potential adjuvant to propofol use in surgical anesthesia. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Biological Potential of Chitinolytic Marine Bacteria
Mar. Drugs 2016, 14(12), 230; doi:10.3390/md14120230
Received: 18 November 2016 / Revised: 7 December 2016 / Accepted: 8 December 2016 / Published: 16 December 2016
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Abstract
Chitinolytic microorganisms secrete a range of chitin modifying enzymes, which can be exploited for production of chitin derived products or as fungal or pest control agents. Here, we explored the potential of 11 marine bacteria (Pseudoalteromonadaceae, Vibrionaceae) for chitin degradation
[...] Read more.
Chitinolytic microorganisms secrete a range of chitin modifying enzymes, which can be exploited for production of chitin derived products or as fungal or pest control agents. Here, we explored the potential of 11 marine bacteria (Pseudoalteromonadaceae, Vibrionaceae) for chitin degradation using in silico and phenotypic assays. Of 10 chitinolytic strains, three strains, Photobacterium galatheae S2753, Pseudoalteromonas piscicida S2040 and S2724, produced large clearing zones on chitin plates. All strains were antifungal, but against different fungal targets. One strain, Pseudoalteromonas piscicida S2040, had a pronounced antifungal activity against all seven fungal strains. There was no correlation between the number of chitin modifying enzymes as found by genome mining and the chitin degrading activity as measured by size of clearing zones on chitin agar. Based on in silico and in vitro analyses, we cloned and expressed two ChiA-like chitinases from the two most potent candidates to exemplify the industrial potential. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Fabrication of Gelatin-Based Electrospun Composite Fibers for Anti-Bacterial Properties and Protein Adsorption
Mar. Drugs 2016, 14(10), 192; doi:10.3390/md14100192
Received: 5 September 2016 / Revised: 14 October 2016 / Accepted: 17 October 2016 / Published: 21 October 2016
Cited by 2 | PDF Full-text (6374 KB) | HTML Full-text | XML Full-text
Abstract
A major goal of biomimetics is the development of chemical compositions and structures that simulate the extracellular matrix. In this study, gelatin-based electrospun composite fibrous membranes were prepared by electrospinning to generate bone scaffold materials. The gelatin-based multicomponent composite fibers were fabricated using
[...] Read more.
A major goal of biomimetics is the development of chemical compositions and structures that simulate the extracellular matrix. In this study, gelatin-based electrospun composite fibrous membranes were prepared by electrospinning to generate bone scaffold materials. The gelatin-based multicomponent composite fibers were fabricated using co-electrospinning, and the composite fibers of chitosan (CS), gelatin (Gel), hydroxyapatite (HA), and graphene oxide (GO) were successfully fabricated for multi-function characteristics of biomimetic scaffolds. The effect of component concentration on composite fiber morphology, antibacterial properties, and protein adsorption were investigated. Composite fibers exhibited effective antibacterial activity against Staphylococcus aureus and Escherichia coli. The study observed that the composite fibers have higher adsorption capacities of bovine serum albumin (BSA) at pH 5.32–6.00 than at pH 3.90–4.50 or 7.35. The protein adsorption on the surface of the composite fiber increased as the initial BSA concentration increased. The surface of the composite reached adsorption equilibrium at 20 min. These results have specific applications for the development of bone scaffold materials, and broad implications in the field of tissue engineering. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Conversion of Squid Pen to Homogentisic Acid via Paenibacillus sp. TKU036 and the Antioxidant and Anti-Inflammatory Activities of Homogentisic Acid
Mar. Drugs 2016, 14(10), 183; doi:10.3390/md14100183
Received: 14 September 2016 / Revised: 5 October 2016 / Accepted: 7 October 2016 / Published: 12 October 2016
Cited by 2 | PDF Full-text (2041 KB) | HTML Full-text | XML Full-text
Abstract
The culture supernatant of Paenibacillus sp. TKU036, a bacterium isolated from Taiwanese soils, showed high antioxidant activity (85%) when cultured in a squid pen powder (SPP)-containing medium at 37 °C for three days. Homogentisic acid (2,5-dihydroxyphenylacetic acid, HGA) was isolated and found to
[...] Read more.
The culture supernatant of Paenibacillus sp. TKU036, a bacterium isolated from Taiwanese soils, showed high antioxidant activity (85%) when cultured in a squid pen powder (SPP)-containing medium at 37 °C for three days. Homogentisic acid (2,5-dihydroxyphenylacetic acid, HGA) was isolated and found to be the major antioxidant in the culture supernatant of the SPP-containing medium fermented by Paenibacillus sp. TKU036. Tryptophan was also present in the culture supernatant. The results of high-performance liquid chromatography (HPLC) fingerprinting showed that HGA and tryptophan were produced via fermentation but did not pre-exist in the unfermented SPP-containing medium. Neither HGA nor tryptophan was found in the culture supernatants obtained from the fermentation of nutrient broth or other chitinous material, i.e., medium containing shrimp head powder, by Paenibacillus sp. TKU036. The production of HGA via microorganisms has rarely been reported. In this study, we found that squid pen was a potential carbon and nitrogen source for Paenibacillus sp. Tryptophan (105 mg/L) and HGA (60 mg/L) were recovered from the culture supernatant. The isolated HGA was found to have higher antioxidant activity (IC50 = 6.9 μg/mL) than α-tocopherol (IC50 = 17.6 μg/mL). The anti-inflammatory activity of the isolated HGA (IC50 = 10.14 μg/mL) was lower than that of quercetin (IC50 = 1.14 μg/mL). As a result, squid pen, a fishery processing byproduct, is a valuable material for the production of tryptophan and the antioxidant and anti-inflammatory HGA via microbial conversion. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Development and Characterization of VEGF165-Chitosan Nanoparticles for the Treatment of Radiation-Induced Skin Injury in Rats
Mar. Drugs 2016, 14(10), 182; doi:10.3390/md14100182
Received: 12 August 2016 / Revised: 30 August 2016 / Accepted: 31 August 2016 / Published: 11 October 2016
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Abstract
Radiation-induced skin injury, which remains a serious concern in radiation therapy, is currently believed to be the result of vascular endothelial cell injury and apoptosis. Here, we established a model of acute radiation-induced skin injury and compared the effect of different vascular growth
[...] Read more.
Radiation-induced skin injury, which remains a serious concern in radiation therapy, is currently believed to be the result of vascular endothelial cell injury and apoptosis. Here, we established a model of acute radiation-induced skin injury and compared the effect of different vascular growth factors on skin healing by observing the changes of microcirculation and cell apoptosis. Vascular endothelial growth factor (VEGF) was more effective at inhibiting apoptosis and preventing injury progression than other factors. A new strategy for improving the bioavailability of vascular growth factors was developed by loading VEGF with chitosan nanoparticles. The VEGF-chitosan nanoparticles showed a protective effect on vascular endothelial cells, improved the local microcirculation, and delayed the development of radioactive skin damage. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Controlling Properties and Cytotoxicity of Chitosan Nanocapsules by Chemical Grafting
Mar. Drugs 2016, 14(10), 175; doi:10.3390/md14100175
Received: 28 July 2016 / Revised: 14 September 2016 / Accepted: 20 September 2016 / Published: 30 September 2016
PDF Full-text (3027 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The tunability of the properties of chitosan-based carriers opens new ways for the application of drugs with low water-stability or high adverse effects. In this work, the combination of a nanoemulsion with a chitosan hydrogel coating and the following poly (ethylene glycol) (PEG)
[...] Read more.
The tunability of the properties of chitosan-based carriers opens new ways for the application of drugs with low water-stability or high adverse effects. In this work, the combination of a nanoemulsion with a chitosan hydrogel coating and the following poly (ethylene glycol) (PEG) grafting is proven to be a promising strategy to obtain a flexible and versatile nanocarrier with an improved stability. Thanks to chitosan amino groups, a new easy and reproducible method to obtain nanocapsule grafting with PEG has been developed in this work, allowing a very good control and tunability of the properties of nanocapsule surface. Two different PEG densities of coverage are studied and the nanocapsule systems obtained are characterized at all steps of the optimization in terms of diameter, Z potential and surface charge (amino group analysis). Results obtained are compatible with a conformation of PEG molecules laying adsorbed on nanoparticle surface after covalent linking through their amino terminal moiety. An improvement in nanocapsule stability in physiological medium is observed with the highest PEG coverage density obtained. Cytotoxicity tests also demonstrate that grafting with PEG is an effective strategy to modulate the cytotoxicity of developed nanocapsules. Such results indicate the suitability of chitosan as protective coating for future studies oriented toward drug delivery. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Novel Spray Dried Glycerol 2-Phosphate Cross-Linked Chitosan Microparticulate Vaginal Delivery System—Development, Characterization and Cytotoxicity Studies
Mar. Drugs 2016, 14(10), 174; doi:10.3390/md14100174
Received: 9 August 2016 / Revised: 13 September 2016 / Accepted: 14 September 2016 / Published: 28 September 2016
PDF Full-text (13829 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for
[...] Read more.
Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human vaginal epithelial cells. The presence of glycerol 2-phosphate influenced drug loading and encapsulation efficacy in chitosan microparticles. By increasing the cross-linking ratio, the microparticles with lower diameter, moisture content and smoother surface were observed. Mucoadhesive studies displayed that all formulations possessed mucoadhesive properties. The in vitro release profile of clotrimazole was found to alter considerably by changing the glycerol 2-phosphate/chitosan ratio. Results from cytotoxicity studies showed occurrence of apoptotic cells in the presence of chitosan and ion cross-linked chitosan microparticles, followed by a loss of membrane potential suggesting that cell death might go through the mitochondrial apoptotic pathway. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Preparation of Chito-Oligomers by Hydrolysis of Chitosan in the Presence of Zeolite as Adsorbent
Mar. Drugs 2016, 14(8), 43; doi:10.3390/md14080043
Received: 31 December 2015 / Revised: 9 February 2016 / Accepted: 15 February 2016 / Published: 23 July 2016
PDF Full-text (1442 KB) | HTML Full-text | XML Full-text
Abstract
An increasing interest has recently been shown to use chitin/chitosan oligomers (chito-oligomers) in medicine and food fields because they are not only water-soluble, nontoxic, and biocompatible materials, but they also exhibit numerous biological properties, including antibacterial, antifungal, and antitumor activities, as well as
[...] Read more.
An increasing interest has recently been shown to use chitin/chitosan oligomers (chito-oligomers) in medicine and food fields because they are not only water-soluble, nontoxic, and biocompatible materials, but they also exhibit numerous biological properties, including antibacterial, antifungal, and antitumor activities, as well as immuno-enhancing effects on animals. Conventional depolymerization methods of chitosan to chito-oligomers are either chemical by acid-hydrolysis under harsh conditions or by enzymatic degradation. In this work, hydrolysis of chitosan to chito-oligomers has been achieved by applying adsorption-separation technique using diluted HCl in the presence of different types of zeolite as adsorbents. The chito-oligomers were retrieved from adsorbents and characterized by differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC/MS), and ninhydrin test. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle The Effect of the Molecular Architecture on the Antioxidant Properties of Chitosan Gallate
Mar. Drugs 2016, 14(5), 95; doi:10.3390/md14050095
Received: 13 March 2016 / Revised: 4 May 2016 / Accepted: 9 May 2016 / Published: 13 May 2016
Cited by 4 | PDF Full-text (2438 KB) | HTML Full-text | XML Full-text
Abstract
To elucidate the structure–antioxidant activity relationships of chitosan gallate (CG), a series of CG derivatives with different degrees of substitution (DS’s) and molecular weights (MWs) were synthesized from chitosan (CS) and gallic acid (GA) via a free radical graft reaction. A higher MW
[...] Read more.
To elucidate the structure–antioxidant activity relationships of chitosan gallate (CG), a series of CG derivatives with different degrees of substitution (DS’s) and molecular weights (MWs) were synthesized from chitosan (CS) and gallic acid (GA) via a free radical graft reaction. A higher MW led to a lower DS of CG. The structures of CG were characterized by FT-IR and 1H NMR, and results showed that GA was mainly conjugated to the C-2 and C-6 positions of the CS chain. The antioxidant activity (the DPPH radical scavenging activity and reducing power) were enhanced with an increased DS and a decreased MW of CG. A correlation between antioxidant activities and the DS and MW of CG was also established. In addition, a suitable concentration (0~250 μg/mL) of CG with different MWs (32.78~489.32 kDa) and DS’s (0~92.89 mg·GAE/g CG) has no cytotoxicity. These results should provide a guideline to the application of CG derivatives in food or pharmacology industries. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Effect of Chitosan Properties on Immunoreactivity
Mar. Drugs 2016, 14(5), 91; doi:10.3390/md14050091
Received: 24 February 2016 / Revised: 15 April 2016 / Accepted: 2 May 2016 / Published: 11 May 2016
Cited by 2 | PDF Full-text (1612 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of
[...] Read more.
Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor-α (TNF-α) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Resonance Rayleigh Scattering Spectra of an Ion-Association Complex of Naphthol Green B–Chitosan System and Its Application in the Highly Sensitive Determination of Chitosan
Mar. Drugs 2016, 14(4), 71; doi:10.3390/md14040071
Received: 29 October 2015 / Revised: 28 March 2016 / Accepted: 29 March 2016 / Published: 18 April 2016
Cited by 2 | PDF Full-text (2382 KB) | HTML Full-text | XML Full-text
Abstract
This work describes a highly-sensitive and accurate approach for the determination of chitosan (CTS) using Naphthol Green B (NGB) as a probe in the Resonance Rayleigh scattering (RRS) method. The interaction between CTS and NGB leads to notable enhancement of RRS, and the
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This work describes a highly-sensitive and accurate approach for the determination of chitosan (CTS) using Naphthol Green B (NGB) as a probe in the Resonance Rayleigh scattering (RRS) method. The interaction between CTS and NGB leads to notable enhancement of RRS, and the enhancement is proportional to the concentration of CTS over a certain range. Under optimum conditions, the calibration curve of ΔI against CTS concentration was ΔI = 1860.5c + 86.125 (c, µg/mL), R2 = 0.9999, and the linear range and detection limit (DL) were 0.01–5.5 µg/mL and 8.87 ng/mL. Moreover, the effect of the molecular weight of CTS on the accurate quantification of CTS was studied. The experimental data were analyzed through linear regression analysis using SPSS20.0, and the molecular weight was found to have no statistical significance. This method has been applied to assay two CTS samples and obtained good recovery and reproducibility. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Chitosan and Kappa-Carrageenan Vaginal Acyclovir Formulations for Prevention of Genital Herpes. In Vitro and Ex Vivo Evaluation
Mar. Drugs 2015, 13(9), 5976-5992; doi:10.3390/md13095976
Received: 2 August 2015 / Revised: 11 September 2015 / Accepted: 15 September 2015 / Published: 18 September 2015
Cited by 4 | PDF Full-text (574 KB) | HTML Full-text | XML Full-text
Abstract
Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations
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Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations have been developed for the controlled release of acyclovir, which may prevent the sexual transmission of the herpes simplex virus. Drug release studies were carried out in two media: simulated vaginal fluid and simulated vaginal fluid/simulated seminal fluid mixture. The bioadhesive capacity and permanence time of the bioadhesion, the prepared compacts, and compacted granules were determined ex vivo using bovine vaginal mucosa as substrate. Swelling processes were quantified to confirm the release data. Biocompatibility was evaluated through in vitro cellular toxicity assays, and the results showed that acyclovir and the rest of the materials had no cytotoxicity at the maximum concentration tested. The mixture of hydroxyl-propyl-methyl-cellulose with chitosan- or kappa-carrageenan-originated mucoadhesive systems that presented a complete and sustained release of acyclovir for a period of 8–9 days in both media. Swelling data revealed the formation of optimal mixed chitosan/hydroxyl-propyl-methyl-cellulose gels which could be appropriated for the prevention of sexual transmission of HSV. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle Physical Stability Studies of Semi-Solid Formulations from Natural Compounds Loaded with Chitosan Microspheres
Mar. Drugs 2015, 13(9), 5901-5919; doi:10.3390/md13095901
Received: 5 August 2015 / Revised: 8 September 2015 / Accepted: 9 September 2015 / Published: 16 September 2015
Cited by 3 | PDF Full-text (1277 KB) | HTML Full-text | XML Full-text
Abstract
A chitosan-based hydrophilic system containing an olive leaf extract was designed and its antioxidant capacity was evaluated. Encapsulation of olive leaf extract in chitosan microspheres was carried out by a spray-drying process. The particles obtained with this technique were found to be spherical
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A chitosan-based hydrophilic system containing an olive leaf extract was designed and its antioxidant capacity was evaluated. Encapsulation of olive leaf extract in chitosan microspheres was carried out by a spray-drying process. The particles obtained with this technique were found to be spherical and had a positive surface charge, which is an indicator of mucoadhesiveness. FTIR and X-ray diffraction results showed that there are not specific interactions of polyphenolic compounds in olive leaf extract with the chitosan matrix. Stability and release studies of chitosan microspheres loaded with olive leaf extract before and after the incorporation into a moisturizer base were performed. The resulting data showed that the developed formulations were stable up to three months. The encapsulation efficiency was around 44% and the release properties of polyphenols from the microspheres were found to be pH dependent. At pH 7.4, polyphenols release was complete after 6 h; whereas the amount of polyphenols released was 40% after the same time at pH 5.5. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

Review

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Open AccessReview Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy
Mar. Drugs 2017, 15(4), 96; doi:10.3390/md15040096
Received: 27 January 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 27 March 2017
Cited by 1 | PDF Full-text (2100 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has
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Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessReview An Overview of the Protective Effects of Chitosan and Acetylated Chitosan Oligosaccharides against Neuronal Disorders
Mar. Drugs 2017, 15(4), 89; doi:10.3390/md15040089
Received: 14 November 2016 / Revised: 7 March 2017 / Accepted: 15 March 2017 / Published: 23 March 2017
PDF Full-text (1180 KB) | HTML Full-text | XML Full-text
Abstract
Chitin is the second most abundant biopolymer on Earth and is mainly comprised of a marine invertebrate, consisting of repeating β-1,4 linked N-acetylated glucosamine units, whereas its N-deacetylated product, chitosan, has broad medical applications. Interestingly, chitosan oligosaccharides have therapeutic effects on different types
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Chitin is the second most abundant biopolymer on Earth and is mainly comprised of a marine invertebrate, consisting of repeating β-1,4 linked N-acetylated glucosamine units, whereas its N-deacetylated product, chitosan, has broad medical applications. Interestingly, chitosan oligosaccharides have therapeutic effects on different types of neuronal disorders, including, but not limited to, Alzheimer’s disease, Parkinson’s disease, and nerve crush injury. A common link among neuronal disorders is observed at a sub-cellular level, such as atypical protein assemblies and induced neuronal death. Chronic activation of innate immune responses that lead to neuronal injury is also common in these diseases. Thus, the common mechanisms of neuronal disorders might explain the general therapeutic effects of chitosan oligosaccharides and their derivatives in these diseases. This review provides an update on the pathogenesis and therapy for neuronal disorders and will be mainly focused on the recent progress made towards the neuroprotective properties of chitosan and acetylated chitosan oligosaccharides. Their structural features and the underlying molecular mechanisms will also be discussed. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessReview Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics
Mar. Drugs 2017, 15(3), 60; doi:10.3390/md15030060
Received: 26 January 2017 / Revised: 21 February 2017 / Accepted: 24 February 2017 / Published: 1 March 2017
Cited by 2 | PDF Full-text (1486 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels,
[...] Read more.
Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessReview “The Good, the Bad and the Ugly” of Chitosans
Mar. Drugs 2016, 14(5), 99; doi:10.3390/md14050099
Received: 14 March 2016 / Revised: 4 May 2016 / Accepted: 9 May 2016 / Published: 17 May 2016
Cited by 12 | PDF Full-text (3138 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this paper is to emphasize the fact that while consistent interest has been paid to the industrial use of chitosan, minor attention has been devoted to spread the knowledge of a good characterization of its physico-chemical properties. Therefore, the paper
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The objective of this paper is to emphasize the fact that while consistent interest has been paid to the industrial use of chitosan, minor attention has been devoted to spread the knowledge of a good characterization of its physico-chemical properties. Therefore, the paper attempts to critically comment on the conflicting experimental results, highlighting the facts, the myths and the controversies. The goal is to indicate how to take advantage of chitosan versatility, to learn how to manage its variability and show how to properly tackle some unexpected undesirable features. In the sections of the paper various issues that relate chitosan properties to some basic features and to advanced solutions and applications are presented. The introduction outlines some historical pioneering works, where the chemistry of chitosan was originally explored. Thereafter, particular reference is made to analytical purity, characterization and chain modifications. The macromolecular characterization is mostly related to molecular weight and to degree of acetylation, but also refers to the conformational and rheological properties and solution stability. Then, the antimicrobial activity of chitosan in relation with its solubility is reviewed. A section is dedicated to the formulation of chitosan biomaterials, from gel to nanobeads, exploring their innovative application as active carrier nanoparticles. Finally, the toxicity issue of chitosan as a polymer and as a constructed nanomaterial is briefly commented in the conclusions. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessFeature PaperReview Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone
Mar. Drugs 2015, 13(12), 7314-7338; doi:10.3390/md13127068
Received: 3 November 2015 / Revised: 22 November 2015 / Accepted: 2 December 2015 / Published: 11 December 2015
Cited by 24 | PDF Full-text (1161 KB) | HTML Full-text | XML Full-text
Abstract
The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of
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The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
Open AccessReview Chitosanases from Family 46 of Glycoside Hydrolases: From Proteins to Phenotypes
Mar. Drugs 2015, 13(11), 6566-6587; doi:10.3390/md13116566
Received: 31 August 2015 / Revised: 9 October 2015 / Accepted: 13 October 2015 / Published: 28 October 2015
Cited by 5 | PDF Full-text (2141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chitosanases, enzymes that catalyze the endo-hydrolysis of glycolytic links in chitosan, are the subject of numerous studies as biotechnological tools to generate low molecular weight chitosan (LMWC) or chitosan oligosaccharides (CHOS) from native, high molecular weight chitosan. Glycoside hydrolases belonging to family GH46
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Chitosanases, enzymes that catalyze the endo-hydrolysis of glycolytic links in chitosan, are the subject of numerous studies as biotechnological tools to generate low molecular weight chitosan (LMWC) or chitosan oligosaccharides (CHOS) from native, high molecular weight chitosan. Glycoside hydrolases belonging to family GH46 are among the best-studied chitosanases, with four crystallography-derived structures available and more than forty enzymes studied at the biochemical level. They were also subjected to numerous site-directed mutagenesis studies, unraveling the molecular mechanisms of hydrolysis. This review is focused on the taxonomic distribution of GH46 proteins, their multi-modular character, the structure-function relationships and their biological functions in the host organisms. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Chitosan-based Multifunctional Platforms for Local Delivery of Drugs
Author: Jaehwi Lee, PhD
Affiliation: Professor of Pharmaceutics and Drug Delivery, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea
Abstract: Chitosan has widely been used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. Especially, chitosan-based microparticles are the most frequently employed dosage forms for the delivery of drugs into the body, along with conventional and specialized delivery systems such as hydrogels, nanoparticle and thin films. Based on the progress made to chitosan-based drug delivery systems, the usefulness of the chitosan has been further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, due to advantageous features of chitosan such as biocompatibility and biodegradability, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessel by which the tumor tissues are supplied with oxygen and nutrients. Indeed, chitosan microspheres have been reported to be as a promising embolic material. For better anti-cancer effect chitosan microspheres that can locally release anti-cancer drugs was proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. Like this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents especially to the specific site of the body. Thus, in this work, case studies where chitosan-based drug delivery systems have successfully been used for the local delivery of therapeutic agents will be presented together with future research and development efforts.

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