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PubMed2006

Chitosan-DNA nanoparticles: the effect of cell type and hydrolysis of chitosan on in vitro DNA transfection.

Commercial chitosan (Ch) with low (LMWCh) and medium molecular weight (MMWCh) were hydrolyzed in diluted hydrochloric acid by heating at different temperatures. The viscosity average molecular weight of Chs was gradually decreased from 450 to 14 kDa as a function of temperature. Ch fractions were used for formation of Ch-DNA nanoparticles and tested for the ability to introduce DNA into HEK293, Swiss3T3, HeLa, and MDCK cells in vitro. The average diameter of nanoparticles was 200-220 nm. The surface charge of nanoparticles varied depending on the Ch/DNA ratio. The cell lines different response to DNA transfection with Ch fractions depended on molecular weight. HEK293 cells were efficiently transfected by nanoparticles prepared with Chs having a wide range of molecular weight (approximately 14-195 kDa). Swiss3T3 cells were efficiently transfected by Ch polymers with about <17 kDa. In contrast, HeLa and MDCK cells were highly resistant to DNA transfection with Ch polymers. These results strongly suggest that Ch polymers may be widely used for DNA trasnfection of the mammalian cells under optimized conditions.

Cell Line↗
PubMed2005

Relevance of molecular weight of chitosan and its derivatives and their antioxidant activities in vitro.

The antioxidant potency of different molecular weight (DMW) chitosan and sulfated chitosan derivatives was investigated employing various established in vitro systems, such as superoxide (O(2)(.-))/hydroxyl ((-.)OH) radicals scavenging, reducing power, iron ion chelating. As expected, we obtained several satisfying results, as follows: firstly, low molecular weight chitosan had stronger scavenging effect on O(2)(.-) and (-.)OH than high molecular weight chitosan. For example the O(2)(.-) scavenging activity of low molecular weight chitosan (9 kDa) and high molecular weight chitosan (760 kDa) were 85.86% and 35.50% at 1.6 mg/mL, respectively. Secondly, comparing with DMW chitosan, DMW sulfated chitosans had the stronger inhibition effect on O(2)(.-). At 0.05 mg/mL, the scavenging activity on O(2)(.-) reached 86.26% for low molecular weight chitosan sulfate (9 kDa), but that of low molecular weight chitosan (9 kDa) was 85.86% at 1.6 mg/mL. As concerning chitosan and sulfated chitosan of the same molecular weight, scavenging activities of sulfated chitosan on superoxide and hydroxyl radicals were more pronounced than that of chitosan. Thirdly, low molecular weight chitosan sulfate had more effective scavenging activity on O(2)(.-) and (-.)OH than that of high molecular weight chitosan sulfate. Fourthly, DMW chitosans and sulfated chitosans were efficient in the reducing power, especially LCTS. Their orders were found to be LCTS>CTS4>HCTS>CTS3>CTS2>CTS1>CTS. Fifthly, CTS4 showed more considerable ferrous ion-chelating potency than others. Finally, the scavenging rate and reducing power of DMW chitosan and sulfated derivatives increased with their increasing concentration. Moreover, change of DMW sulfated chitosans was the most pronounced within the experimental concentration. However, chelating effect of DMW chitosans were not concentration dependent except for CTS4 and CTS1.

Antioxidants↗
PubMed2005

Preparation and evaluation of a chitosan salt-poloxamer 407 based matrix for buccal drug delivery.

The aim of this work was to prepare and evaluate a matrix for buccal drug delivery composed of a chitosan salt and poloxamer 407. Different chitosan salts were formed by reacting chitosan with acetic, citric, and lactic acid. Various proportions of poloxamer 407 were added to the aqueous solution of chitosan salt, and the residue obtained by lyophilisation was compressed into discs, using a 30 kN compression force. An experimental design (3(2)) was used to study the influence of the type of chitosan salt and of the relative amount of poloxamer on drug release capacity, swelling, erosion, and mucoadhesiveness of matrices. The results showed that matrix properties depended significantly on both relative amount of poloxamer and chitosan salt type. The rank orders of chitosan salts for the four processes evaluated were as follows: drug release: chitosan acetate>chitosan citrate>chitosan lactate; swelling: chitosan lactate>chitosan acetate=chitosan citrate; erosion: chitosan citrate>chitosan lactate>chitosan acetate; mucoadhesion: chitosan lactate>chitosan acetate=chitosan citrate. Mucoadhesion was particularly favoured when poloxamer 407 was present at about 30% (w/w). The matrix composed of chitosan lactate and poloxamer 407 showed the best characteristics for buccal administration.

Administration, Buccal↗
PubMed2006

Chitosan-g-PEG/DNA complexes deliver gene to the rat liver via intrabiliary and intraportal infusions.

BACKGROUND: Chitosan has been shown to be a non-toxic and efficient vector for in vitro gene transfection and in vivo gene delivery through pulmonary and oral administrations. Recently, we have shown that chitosan/DNA nanoparticles could mediate high levels of gene expression following intrabiliary infusion 1. In this study, we have examined the possibility of using polyethylene glycol (PEG)-grafted chitosan/DNA complexes to deliver genes to the liver through bile duct and portal vein infusions. METHODS: PEG (Mw: 5 kDa) was grafted onto chitosan (Mw: 47 kDa, deacetylation degree: 94%) with grafting degrees of 3.6% and 9.6% (molar percentage of chitosan monosaccharide units grafted with PEG). The stability of chitosan-g-PEG/DNA complexes was studied by measuring the change in particle size and by agarose gel electrophoresis against bile or serum challenge. The influence of PEG grafting on gene transfection efficiency was evaluated in HepG2 cells using luciferase reporter gene. Chitosan and chitosan-g-PEG/DNA complexes were delivered to the liver through bile duct and portal vein infusions with a syringe pump. Gene expression in the liver and the distribution of gene expression in other organs were evaluated. The acute liver toxicity of chitosan and chitosan-g-PEG/DNA complexes was examined by measuring serum alanine aminotranferase (ALT) and aspartate aminotransferase (AST) activities as a function of time. RESULTS: Both chitosan and chitosan-g-PEG displayed comparable gene transfection efficiency in HepG2 cells. After challenge with serum and bile, chitosan-g-PEG/DNA complexes, especially those prepared with chitosan-g-PEG (GD = 9.6%), did not form large aggregates like chitosan/DNA complexes but remained stable for up to 30 min. In addition, chitosan-g-PEG prevented the degradation of DNA in the presence of serum and bile. On day 3 after bile duct infusion, chitosan-g-PEG (GD = 9.6%)/DNA complexes mediated three times higher gene expression in the liver than chitosan/DNA complexes and yielded background levels of gene expression in other organs. On day 1 following portal vein infusion, gene expression level induced by chitosan/DNA complexes was hardly detectable but chitosan-g-PEG (GD = 9.6%) mediated significant transgene expression. Interestingly, transgene expression by chitosan-g-PEG/DNA complexes in other organs after portal vein infusion increased with increasing grafting degree of PEG. The ALT and AST assays indicated that grafting of PEG to chitosan reduced the acute liver toxicity towards the complexes. CONCLUSION: This study demonstrated the potential of chitosan-g-PEG as a safe and more stable gene carrier to the liver.

Animals↗
PubMed2004

Antitumor effects of various low-molecular-weight chitosans are due to increased natural killer activity of intestinal intraepithelial lymphocytes in sarcoma 180-bearing mice.

Various low-molecular-weight chitosans such as the 21-kDa, 46-kDa, and 120-kDa chitosans obtained by enzymatic hydrolysis of a high-molecular-weight chitosan (average molecular weight, 650 kDa) had low viscosity and were water soluble. We examined the antitumor activity of various water-soluble chitosans with different molecular weights in sarcoma 180-bearing mice. A 21-kDa water-soluble chitosan and oligochitosan (100 and 300 mg/kg body) administered by i.g. intubation reduced the tumor growth and final tumor weight in sarcoma 180-bearing mice. A 46-kDa water-soluble chitosan at a dose of 100 mg/kg body reduced the tumor growth and final tumor weight, but had no effect at 300 mg/kg. On the other hand, a 130-kDa water-soluble chitosan had no effect on tumor growth. The 21- and 46-kDa chitosans (10 mg/L) enhanced the natural killer (NK) activity in intestinal intraepithelial lymphocytes (IELs) or splenic lymphocytes. The NK activity of low-molecular-weight chitosan (21- and 46-kDa chitosans)-treated IELs or splenic lymphocytes was stronger than that of high-molecular-weight chitosan (130- and 650-kDa chitosans)-treated IELs or splenic lymphocytes. In addition, low-molecular-weight chitosan-treated IELs or splenic lymphocytes also enhanced the cytotoxic activity against sarcoma 180 cells. In an in vivo study, although low-molecular-weight chitosan-treated IELs had cytotoxic activity against tumor cells, splenic lymphocytes treated with chitosans had no effect. These findings suggest that the antitumor activity of low-molecular-weight chitosans (12- and 46-kDa chitosans) and oligochitosan might be due in part to the enhancement of NK activity in IELs. Thus, the low-molecular-weight chitosans or oligochitosan might be useful in preventing tumor growth through the activation of intestinal immune functions.

Adjuvants, Pharmaceutic↗
PubMed2005

[The role of local immune response in gastric mucosa in the protection induced by Helicobacter pylori vaccine with chitosan as adjuvant].

OBJECTIVE: To study the immunological protection of Helicobacter pylori (H. pylori) vaccine with chitosan as adjuvant and it's mechanism. METHODS: One-grade female BALB/c mice were randomly divided into nine groups and immunized by (1) PBS alone, (2) chitosan solution alone, (3) chitosan particles alone, (4) H. pylori antigen alone, (5) H. pylori antigen plus chitosan solution, (6) H. pylori antigen plus chitosan particles, (7) H. pylori antigen plus CT, (8) H. pylori antigen plus chitosan solution and cholera toxin (CT), (9) H. pylori antigen plus chitosan particles and CT orally respectively once a week for four weeks. At 4 weeks after the last immunization, these mice were challenged by alive H. pylori (1 x 10(9)/ml) twice at two days intervals. At 4 weeks after the last challenge, these mice were all killed and Gastric mucosa were embedded in paraffin, sectioned and assayed with Giemsa stain. The other gastric mucosa were used to quantitatively culture H. pylori. An ELISA was used to detect anti-H. pylori IgA in saliva and gastric mucosa and a quantitative ELISA was used to detect IL-2, IL-4, IL-10 content in gastric mucosa, and SP immunohistochemical method was used to detect secretory immunoglobulin A (sIgA) in gastric mucosa. RESULTS: (1) In the groups with chitosan as adjuvant, 60% mice could achieve immunological protection, which was according to that with CT as adjuvant (58.33%), and was significantly higher than H. pylori antigen alone and other groups without H. pylori antigen (P < 0.01 or P < 0.05). While the rates of protection in the groups with chitosan plus CT as adjuvant were 84.62%, 85.71% and the H. pylori colonization score in it was significantly lower than that in the groups with CT as adjuvant and without adjuvants (P < 0.01 or P < 0.05). (2) the labeling index for sIgA-positive lumen of glands and special anti-H. pylori IgA levels in gastric mucosa in the groups with chitosan as an adjuvant had no difference with those in the group with CT as an adjuvant (P > 0.05) and were significantly higher than those in non-adjuvant groups, while those in the groups with chitosan plus CT were significantly higher than those in the group with CT as an adjuvant (P < 0.01 or P < 0.05). (3) Before challenge, the content of IL-2 in gastric mucosa were no different among different groups (P > 0.05). After challenge the content of IL-2 were significantly higher in the groups with adjuvant than those in the control group (P < 0.01 or P < 0.05), Moreover, those in the groups with antigen after challenge were significantly higher than those before challenge (P < 0.05). (4) Before challenge, the content of IL-10 in gastric mucosa were significantly higher in the groups with chitosan as adjuvant than those in the control group and the group without adjuvant (P < 0.01 or P < 0.05). After challenge, the content of IL-10 were no different among different groups (P > 0.05). Moreover, those in the groups with adjuvant after challenge were significantly lower than those before challenge (P < 0.01). (5) Before challenge, the content of IL-4 in gastric mucosa were significantly higher in the groups with chitosan as adjuvant than those in the control group and the group without adjuvant (P < 0.05), After challenge, the content of IL-4 were significantly higher in the groups with chitosan particles as an adjuvant than those in the group with CT as an adjuvant (P < 0.05), and those in the group with chitosan solution as an adjuvant were significantly higher than those in control group, non-adjuvant group and the groups with CT (P < 0.01 or P < 0.05), Moreover, those in the groups with adjuvant after challenge were significantly lower than those before challenge (P < 0.01 or P < 0.05). CONCLUSIONS: (1) H. pylori vaccine with chitosan as adjuvant could protect against H. pylori infection, this suggested that chitosan could be a mucosa adjuvant of H. pylori vaccine, and it could effectively elicit special humoral immune response of systemic and local mucosa, which might be one of its protective mechanism. (2) H. pylori vaccine with chitosan as adjuvant may induce both Th1 and Th2 type immune response, and after challenge it could reverse the inhibition of Th2 induced by H. pylori infection and recover the Th1/Th2 imbalance. which might contribute to the immune protection against H. pylori.

Adjuvants, Immunologic↗
PubMed2002

Growth of human endothelial cells on photochemically grafted Gly-Arg-Gly-Asp (GRGD) chitosans.

To improve ECs adhesion and growth on chitosan, cell adhesive peptide Gly-Arg-Gly-Asp (GRGD) was photochemically grafted to its surface. Grafting 0.025 M of GRGD-SANPAH (N-Succinimidyl-6-[4'-azido-2'-nitrophenylamino]-hexanoate) solutions to chitosan and tripolyphosphate anhydrous crosslinked chitosan (chitosan-TPP) surfaces was performed by surface adsorption of the peptide and subsequent ultraviolet (UV) irradiation for photoreaction. FTIR spectra and electron spectroscopy for chemical analysis (ESCA) confirmed that GRGD was successfully grafted to form chitosan-GRGD surfaces (e.g., the composition fraction of nitrogen (N(1s)) for chitosan-GRGD surface was 5.2% instead of 3.2% for chitosan only). Moreover, the grafting efficiencies for 0.025 M of GRGD to chitosan and chitosan-TPP surfaces were about 83% and 53%, semi-quantitatively analyzed by an HPLC. Human umbilical vein ECs were well adhered and grew on chitosan-GRGD and chitosan-TPP-GRGD surfaces after 36 h of incubation but not chitosan and chitosan-TPP ones. Moreover, the viability for the growth of ECs on the chitosan-GRGD and chitosan-TPP-GRGD surfaces analyzed by MTT assay also confirmed the efficacy of the GRGD immobilization. In conclusion, the chitosan-GRGD and chitosan-TPP-GRGD surfaces were prepared by a photochemical technique that could enhance the adhesion and growth of ECs on those surfaces for further applications for tissue engineering.

Biocompatible Materials↗
PubMed2005

Preparation and important functional properties of water-soluble chitosan produced through Maillard reaction.

The objective of this research was to improve the solubility of chitosan at neutral or basic pH using the Maillard-type reaction method. To prepare the water-soluble chitosans, various chitosans and saccharides were used under various operating conditions. Biological and physicochemical properties of the chitosan-saccharide derivatives were investigated as well. Results indicated that the solubility of modified chitosan is significantly greater than that of native chitosan, and the chitosan-maltose derivative remained soluble when the pH approached 10. Among chitosan-saccharide derivatives, the solubility of chitosan-fructose derivative was highest at 17.1 g/l. Considering yield, solubility and pH stability, the chitosan-glucosamine derivative was deemed the optimal water-soluble derivative. Compared with the acid-soluble chitosan, the chitosan-glucosamine derivative exhibited high chelating capacity for Zn(2+), Fe(2+) and Cu(2+) ions. Relatively high antibacterial activity against Escherichia coli and Staphylococcus aureus was noted for the chitosan-glucosamine derivative as compared with native chitosan. Results suggest that the water-soluble chitosan produced using the Maillard reaction may be a promising commercial substitute for acid-soluble chitosan.

Anti-Bacterial Agents↗
PubMedDate not supplied

Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing.

PURPOSE: To investigate the suitability of chitosan films prepared using two different solvents, acetic acid (Chitosan-AA) and lactic acid (Chitosan-LA), for wound dressing, in comparison with a commercial preparation, Omiderm. METHODS: The mechanical and in-vitro bioadhesive strength properties of Chitosan-AA, Chitosan-LA, and Omiderm were investigated using texture analyzer equipment. The vapour permeability of chitosan films was determined using a method for evaluation of moisture permeability of containers and packaging material described in USP XXII. In addition, the biological evaluations were performed via primary skin irritation, intracutaneous, and systemic injection tests. RESULTS: The three preparations differed significantly in terms of the mechanical and bioadhesive strength properties. Chitosan-LA exhibited a lower tensile strength, but more flexible and bioadhesive than Chitosan-AA. Chitosan film was found to be permeable to water vapour. Chitosan-LA and Omiderm were non-irritant and did not cause any skin allergic reaction. In contrast, Chitosan-AA films inflicted adverse skin reactions. Nevertheless, no gross sign of toxicity was encountered from the systemic injection of the extracts of the three preparations. CONCLUSION: Chitosan films demonstrated significantly different mechanical and bioadhesive strength properties from Omiderm. Chitosan-LA was more soft, flexible, pliable and bioadhesive when compared to Chitosan-AA films. Furthermore, Chitosan-LA did not cause erythema, edema and systemic toxicity. Hence, Chitosan-LA film is suitable to be used in the management of wound healing and skin burn.

Acetylation↗
PubMed1999

Chitosans as absorption enhancers of poorly absorbable drugs. 3: Influence of mucus on absorption enhancement.

Chitosans are potent nontoxic absorption enhancers after nasal administration but their effects on the intestinal epithelium in vivo has not been studied in detail. In this study, the effects of chitosans with varying molecular weights and degrees of acetylation on the absorption of a poorly absorbed model drug (atenolol) were studied in intestinal epithelial cell layers with or without a mucus layer and in an in situ perfusion model of rat ileum. The effects of the chitosans on epithelial morphology and release of lactate dehydrogenase (LDH) into the perfusate were investigated in the in situ model. The chitosans had pronounced effects on the permeability of mucus-free Caco-2 layers and enhanced the permeation of atenolol 10- to 15-fold, with different absorption kinetics for different chitosans, in accordance with previous results. In contrast, enhancement of atenolol absorption through rat ileum was modest. LDH release from the tissues perfused with chitosans did not increase, indicating that the chitosans were used at nontoxic concentrations. Morphological examination of the perfused ileal tissues revealed more mucus discharge from the tissues exposed to chitosans than from controls, which suggested that the discharged mucus may inhibit the binding of chitosan to the epithelial surface and hence decrease the absorption-enhancing effect. This hypothesis was supported by studies with intestinal epithelial HT29-H goblet cells covered with a mucus layer. The binding of chitosan to the epithelial cell surface and subsequent absorption-enhancing effects were significantly reduced in mucus-covered HT29-H cultures. When the mucus layer was removed prior to the addition of chitosan, the cell surface binding and absorption-enhancing effects of the chitosans were increased. We conclude that the modest absorption-enhancing effects of unformulated chitosan solutions in the perfused rat ileum are a result of the mucus barrier in this tissue. This effect may be overcome by increasing the local concentrations of both chitosan and drug, i.e,. through formulation of the chitosan into a particulate dosage form.

Adrenergic beta-Antagonists↗
PubMed2004

Thiolated chitosans.

The derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions leads to the formation of thiolated chitosans. So far, three types of thiolated chitosans have been generated: chitosan-cysteine conjugates, chitosan-thioglycolic acid conjugates and chitosan-4-thio-butyl-amidine conjugates. Various properties of chitosan are improved by this immobilization of thiol groups. Due to the formation of disulfide bonds with mucus glycoproteins, the mucoadhesiveness is 6--100-fold augmented (I). The permeation of paracellular markers through intestinal mucosa can be enhanced 1.6--3-fold utilizing thiolated instead of unmodified chitosan (II). Moreover, thiolated chitosans display in situ-gelling features, due to the pH-dependent formation of inter- as well as intra-molecular disulfide bonds (III). This latter process provides a strong cohesion and stability of carrier matrices being based on thiolated chitosans (IV). Consequently, thiolated chitosans can guarantee a prolonged controlled release of embedded therapeutic ingredients (V). The potential of thiolated chitosans has meanwhile also been demonstrated in vivo. A significant pharmacological efficacy of 1.3% of orally given salmon calcitonin, for instance, could be achieved utilizing thiolated chitosan as polymeric drug carrier matrix, while no effect was reached using unmodified chitosan. According to these results thiolated chitosans represent a promising new category of polymeric excipients in particular for the non-invasive administration of hydrophilic macromolecules. Further applications such as their use as scaffold materials in tissue engineering or as coating material for stents seem feasible.

Animals↗
PubMed2001

Synthesis and antibacterial activities of quaternary ammonium salt of chitosan.

Chitosan derivatives with quaternary ammonium salt, such as N,N,N-trimethyl chitosan, N-N-propyl-N,N-dimethyl chitosan and N-furfuryl-N,N-dimethyl chitosan were prepared using different 96% deacetylated chitosan of M(v) 2.14x10(5), 1.9x10(4), 7.8x10(3). Amino groups on chitosan react with aldehydes to from a Schiff base intermediate. Quaternized chitosan were obtained by reaction of a Schiff base with methyl iodide. The yields, degree of quaternization and water-solubility of quaternized chitosan were influenced by the molecular weight of the chitosan sample. The antibacterial activities of quaternized chitosan against Escherichia coli were explored by calculation of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in water, 0.25 and 0.50% acetic acid medium. Results show the antibacterial activities of quaternized chitosan against E. coli is related to its molecular weight. Antibacterial activities of quaternized chitosan in acetic acid medium is stronger than that in water. Their antibacterial activities is increased as the concentration of acetic acid is increased. It was also found that the antibacterial activity of quaternized chitosan against E. coli is stronger than that of chitosan.

Alkylation↗
PubMed2002

Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials.

For the purpose of obtaining high bone forming efficacy, development of chitosan was attempted as a tool useful as a scaffolding device. Porous chitosan matrices, chitosan-poly(L-lactide) (PLLA) composite matrices and chitosan coated on PLLA matrices were dealt with in this research. Porous chitosan matrix was fabricated by freeze-drying and cross-linking aqueous chitosan solution. Porous chitosan matrix combined with ceramics and constituents of extracellular matrices were prepared and examined for their bone regenerative potential. Composite porous matrix of chitosan-PLLA was prepared by mixing polylactide with chitosan and freeze-drying. All chitosan based devices demonstrated improved bone forming capacity by increasing mechanical stability and biocompatibility. Release of platelet-derived growth factor-BB (PDGF-BB) from these matrices exerted significant osteoinductive effect in addition to the high osteoconducting capacity of the porous chitosan matrices. The hydrophobic surface of PLLA matrices was modified by chitosan to enhance cell affinity and wettability. The chitosan coated PLLA matrix induced increased osteoblast attachment as compared with intact PLLA surface. Overall results in this study demonstrated the usefulness of chitosan as drug releasing scaffolds and as modification tools for currently used biomaterials to enhance tissue regeneration efficacy. These results may expand the feasibility of combinative strategy of controlled local drug delivery concept and tissue engineered bone formation in reconstructive therapy in the field of periodontics, orthopedics and plastic surgery.

Animals↗
PubMed1997

Chitosan functional properties.

Chitosan is a partially deacetylated polymer of N-acetyl glucosamine. It is essentially a natural, water-soluble, derivative of cellulose with unique properties. Chitosan is usually prepared from chitin (2 acetamido-2-deoxy beta-1,4-D-glucan) and chitin has been found in a wide range of natural sources (crustaceans, fungi, insects, annelids, molluscs, coelenterata etc.) However chitosan is only manufactured from crustaceans (crab and crayfish) primarily because a large amount of the crustacean exoskeleton is available as a by product of food processing. Squid pens (a waste byproduct of New Zealand squid processing) are a novel, renewable source of chitin and chitosan. Squid pens are currently regarded as waste and so the raw material is relatively cheap. This study was intended to assess the functional properties of squid pen chitosan. Chitosan was extracted from squid pens and assessed for composition, rheology, flocculation, film formation and antimicrobial properties. Crustacean chitosans were also assessed for comparison. Squid chitosan was colourless, had a low ash content and had significantly improved thickening and suspending properties. The flocculation capacity of squid chitosan was low in comparison with the crustacean sourced chitosans. However it should be possible to increase the flocculation capacity of squid pen chitosan by decreasing the degree of acetylation. Films made with squid chitosan were more elastic than crustacean chitosan with improved functional properties. This high quality chitosan could prove particularly suitable for medical/analytical applications.

Animals↗
PubMed2005

Chitosan and sodium sulfate as excipients in the preparation of prolonged release theophylline tablets.

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.

Animals↗
PubMed2006

Fast setting calcium phosphate cement-chitosan composite: mechanical properties and dissolution rates.

Calcium phosphate cement (CPC) can self-harden in vivo to form hydroxyapatite (HA) with excellent osteoconductivity. In recent studies, CPC-chitosan composites are developed with high mechanical strength and washout resistance. The objectives of the present study are to optimize the setting time and mechanical properties of a CPC-chitosan composite by tailoring the chitosan content, and to evaluate the bioresorbability by using an in vitro dissolution model. Six chitosan mass fractions are tested: 0, 10, 15, 20, 25, and 30%. Specimens are immersed in solutions with pH ranging from 3.5 to 5 to simulate the acidic environments produced by osteoclasts in vivo. Dissolution is measured as the fraction of mass loss versus immersion time from 7d to 28d. The CPC-chitosan composite with 20% by mass chitosan has a setting time (mean+/-SD; n=4) of 13 1 min, significantly less than 87 7 min for CPC control without chitosan (p<0.05). The composite flexural strength (mean+/-SD; n 1/4 6) was 14 2 MPa, significantly higher than 4 1 MPa of CPC control (p<0.05). At an intermediate pH of 4.5, the fraction of mass loss for CPC with 20% chitosan and CPC control without chitosan are not significantly different (p>0.1). The dissolution rates (fraction of mass loss per day,%/d) were 1.05 for CPC control and 1.08 for CPC-chitosan. In summary, a CPC-chitosan composite is developed with fast-setting and a flexural strength three-fold of that of CPC control without chitosan. Both materials are soluble in acidic environments, indicating that adding chitosan did not compromise the bioresorbability of CPC. The strong and resorbable CPC-chitosan composite may be useful in moderate stress-bearing craniofacial and orthopedic repairs.

Bone Cements↗