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Biomedical subjects

E Khor

Publications and source records attributed to E Khor.

At least 19 recordsLinked to original sources

Characterization of chitosan acetate as a binder for sustained release tablets.

A chitosan derivative as an acetate salt was successfully prepared by using a spray drying technique. Physicochemical characteristics and micromeritic properties of spray-dried chitosan acetate (SD-CSA) were studied as well as drug-polymer and excipient-polymer interaction. SD-CSA was spherical agglomerates with rough surface and less than 75 microm in diameter. The salt was an amorphous solid with slight to moderate hygroscopicity. The results of Fourier transform infrared (FTIR) and solid-state (13)C NMR spectroscopy demonstrated the functional groups of an acetate salt in its molecular structure. DSC and TGA thermograms of SD-CSA as well as FTIR and NMR spectrum of the salt, heated at 120 degrees C for 12 h, revealed the evidence of the conversion of chitosan acetate molecular structure to N-acetylglucosamine at higher temperature. No interaction of SD-CSA with either drugs (salicylic acid and theophylline) or selected pharmaceutical excipients were observed in the study using DSC method. As a wet granulation binder, SD-CSA gave theophylline granules with good flowability (according to the value of angle of repose, Carr's index, and Hausner ratio) and an excellent compressibility profile comparable to a pharmaceutical binder, PVP K30. In vitro release study of theophylline from the tablets containing 3% w/w SD-CSA as a binder demonstrated sustained drug release in all media. Cumulative drug released in 0.1 N HCl, pH 6.8 phosphate buffer and distilled water was nearly 100% within 6, 16 and 24 h, respectively. It was suggested that the simple incorporation of spray-dried chitosan acetate as a tablet binder could give rise to controlled drug delivery systems exhibiting sustained drug release.

Chitosan↗

Concurrent production of chitin from shrimp shells and fungi.

Crustacean shells constitute the traditional and current commercial source of chitin. Conversely, the control of fungal fermentation processes to produce quality chitin makes fungal mycelia an attractive alternative source. Therefore, the exploitation of both of these sources to produce chitin in a concurrent process should be advantageous and is reported here. Three proteolytic Aspergillus niger (strains 0576, 0307 and 0474) were selected from a screening for protease activity from among 34 zygomycete and deuteromycete strains. When fungi and shrimp shell powder were combined in a single reactor, the release of protease by the fungi facilitated the deproteinization of shrimp-shell powder and the release of hydrolyzed proteins. The hydrolyzed proteins in turn were utilized as a nitrogen source for fungal growth, leading to a lowering of the pH of the fermentation medium, thereby further enhancing the demineralization of the shrimp-shell powder. The shrimp-shell powders and fungal mycelia were separated after fermentation and extracted for chitin with 5% LiCl/DMAc solvent. Chitin isolates from the shells were found to have a protein content of less than 5%, while chitin isolates from the three fungal mycelia strains had protein content in the range of 10-15%. The relative molecular weights as estimated by GPC for all chitin samples were in the 10(5) dalton range. All samples displayed characteristic profiles for chitin in their FTIR and solid-state NMR spectra. All chitin samples evaluated with MTT and Neutral Red assays with three commercial cell lines did not display cytotoxic effects.

Animals↗

Preparation and characterization of chitin beads as a wound dressing precursor.

Chitin was dissolved in N, N-dimethylacetamide/5% lithium chloride (DMAc/5%LiCl) to form a 0.5% chitin solution. Chitin beads were formed by dropping the 0.5% chitin solution into a nonsolvent coagulant, ethanol. The beads were left in ethanol for 24 h to permit hardening, consolidation, and removal of residual DMAc/5%LiCl solvent in order to give spherical chitin beads uniform size distribution. The ethanol-gelled chitin beads had an average diameter of 535 microm. The chitin beads were subsequently activated in 50% (w/v) NaOH solution and reacted with 1.9 M monochloroacetic acid/2-propanol solution to introduce a carboxymethylated surface layer to the chitin beads. The bilayer character of the surface-carboxymethylated chitin (SCM-chitin) beads was verified by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and confocal microscopy. The bilayered SCM-chitin beads were found to absorb up to 95 times their dry weight of water. These SCM-chitin beads have potential as a component of wound dressings.

Algorithms↗

Chitosan-alginate films prepared with chitosans of different molecular weights.

Chitosan-alginate polyelectrolyte complex (CS-AL PEC) is water insoluble and more effective in limiting the release of encapsulated materials compared to chitosan or alginate. Coherent CS-AL PEC films have been prepared in our laboratory by casting and drying suspensions of chitosan-alginate coacervates. The objective of this study was to evaluate the properties of the CS-AL PEC films prepared with chitosans of different molecular weights. Films prepared with low-molecular-weight chitosan (Mv 1.30 x 10(5)) were twice as thin and transparent, as well as 55% less permeable to water vapor, compared to films prepared with high-molecular-weight chitosan (Mv 10.0 x 10(5)). It may be inferred that the low-molecular-weight chitosan reacted more completely with the sodium alginate (M(v) 1.04 x 10(5)) than chitosan of higher molecular weight. A threshold molecular weight may be required, because chitosans of Mv 10.0 x 10(5) and 5.33 x 10(5) yielded films with similar physical properties. The PEC films exhibited different surface properties from the parent films, and contained a higher degree of chain alignment with the possible formation of new crystal types. The PEC films exhibited good in vitro biocompatibility with mouse and human fibroblasts, suggesting that they can be further explored for biomedical applications.

Animals↗

Chitosan-alginate-CaCl(2) system for membrane coat application.

Water-based formulations are preferred for membrane coat application because they do not require the use of noxious solvents. A novel aqueous chitosan-alginate-CaCl(2) system was evaluated as a potential formulation to produce water-insoluble membranes of biodegradable polymers. Chitosan-alginate coacervates were prepared by controlled reaction of chitosan (0.25% w/v) and sodium alginate (0.25% w/v) solutions. Coherent membranes were obtained by casting and drying the coacervates suspended in aqueous CaCl(2) solutions (0.05-0.07% w/v). Increasing the calcium content did not modify membrane thickness (25-26 microm), but reduced the water vapor transmission rate from 658 to 566 g/m(2)/day, and improved the tensile strength of the membranes from 9.33 to 17.13 MPa. Differential scanning calorimetry, Fourier transform infrared spectroscopy, and elemental analyses of the chitosan-alginate coacervates indicated they were stable for up to 4 weeks of storage in distilled water at ambient temperature. Membranes of the stored coacervates required less calcium to attain maximum mechanical strength. They also had higher water vapor transmission rates than corresponding films prepared from fresh coacervates. On the basis of the properties of the cast film and its storage stability, the chitosan-alginate-CaCl(2) system can be considered for potential membrane coat application.

Alginates↗

Wound dressing with sustained anti-microbial capability.

To overcome current limitations in wound dressings for treating mustard-burn induced septic wound injuries, a nonadherent wound dressing with sustained anti-microbial capability has been developed. The wound dressing consists of two layers: the upper layer is a carboxymethyl-chitin hydrogel material, while the lower layer is an anti-microbial impregnated biomaterial. The hydrogel layer acts as a mechanical and microbial barrier, and is capable of absorbing wound exudate. In physiological fluid, the carboxymethylated-chitin hydrogel swells considerably, imbibing up to 4 times its own weight of water and is also highly porous to water vapor. The moisture permeability of the dressing prevents the accumulation of fluid in heavily exudating wounds seen in second-degree burns. The lower layer, fabricated from chitosan acetate foam, is impregnated with chlorhexidine gluconate. From the in vitro release studies, the loading concentration was optimized to deliver sufficient anti-microbial drug into the wound area to sustain the anti-microbial activity for 24 h. The anti-microbial activity of the dressing against Pseudomonas aeruginosa and Staphylococcus aureus was tested using the Bauer-Kirby Disk Diffusion Test.

Anti-Infective Agents↗

Novel fabrication of open-pore chitin matrixes.

A novel method has been developed to produce open-pore chitin matrixes. Chitin solutions were loaded with calcium carbonate (CaCO3) crystals and the mixture cast to form gels. The CaCO3-chitin gels were submerged in 1 N HCl solution to produce highly porous matrixes with good water vapor permeability, water uptake profile, and enhanced mechanical properties. The open-pore system is obtainable because CaCO3 loaded into the chitin gel reacts with 1 N HCl solution to produce gaseous carbon dioxide. Evolution of carbon dioxide during the reaction results in continuous pore structures from the matrix' bulk to surface. When the concentration of CaCO3 loaded into the chitin gel is controlled, defined homogeneous pores measuring 100-500 and 500-1000 microns, with porosities of approximately 76% and 81%, respectively, can be produced.

Calcium Carbonate↗

Invasive Haemophilus influenzae type b infections in Singapore children: a hospital-based study.

OBJECTIVE: A 6-year (1990-95) hospital-based retrospective study was carried out to investigate the pattern of invasive Haemophilus influenzae type b (Hib) disease. METHODOLOGY: Cases with Hib isolated from sterile sites (blood, cerebrospinal fluid, or joint aspirate) were identified from the hospital's microbiological records, and their reviewed case records. Patients with pyogenic meningitis in the same study period were also identified to estimate the incidence of Hib meningitis. RESULTS: Twelve patients had positive cultures from sterile sites, of whom nine children were less than 5 years of age. These included seven cases of meningitis, one patient with acute epiglottitis, and one case of pneumonia. Three of the seven patients with meningitis had significant long-term sequelae. Our data also suggests a relatively low proportion of ethnic Chinese children with invasive disease. It was estimated that 18.4% to 41.1% of pyogenic meningitis in children admitted to the National University Hospital were due to Hib. The estimated annual attack rate of invasive Hib disease was at most 3.3 per 100 000 children aged less than 5 years (95% confidence interval: 2.6-3.5/100 000). CONCLUSION: : Invasive Hib infections are relatively uncommon in our community. This justifies the need for a cost effectiveness study before a universal Hib vaccination program is implemented.

Child, Preschool↗

PEC films prepared from Chitosan-Alginate coacervates.

Chitosan-alginate polyelectrolyte complex (PEC) have been prepared in situ in beads and microspheres. This study examines the preparation of suitable chitosan-alginate coacervates for casting into homogeneous PEC films for potential applications in packaging, controlled release systems and wound dressings. Coacervation between chitosan and alginate was rapid, but the rate may be controlled with the addition of water miscible organic solvents. Compared with ethanol and PEG200, acetone was the more promising solvent moderator. Suspensions of fine, uniformly dispersed coacervates were produced by a dropwise addition of 0.25% w/v chitosan solution (solvent: 1: 1 v/v of 2% acetic acid and acetone) into 0.25% w/v sodium alginate solution in water under rapid agitation. The PEC films were transparent and flexible. They exhibited high permeability to water vapor, but resisted complete dissolution in 0.1 M HCI, distilled water and pH 7.4 phosphate buffer solution. Microscopic heterogeneity in the films could be reduced by immersion in aqueous media, but this was accompanied by modifications in the thickness, permeability and mechanical property of the films.

Alginates↗

Effects of dry heat and saturated steam on the physical properties of chitosan.

Heat may be employed to facilitate the processing of chitosan and to confer sterility on chitosan-based medical products. In this study, changes were analyzed of the physical properties of purified chitosan heated at 60 to 160 degrees C under specified conditions for periods ranging from 0.5 to 4 h. Two forms of heat were used for processing: dry heat generated by a convection oven and saturated steam generated by an autoclave. Dry heat at < or = 80 degrees C resulted in less rigid chains with lower glass transition temperature, improved aqueous solubility, and slightly higher [eta]. At higher temperatures, dry heat produced chromophores, which may be related to interchain crosslink formation involving the NH2 groups. The [eta] and aqueous solubility of the samples decreased with temperatures > or = 120 degrees C. The coloration of the samples intensified from yellow to brown with increasing temperatures and duration of heat exposure. Chitosan heated at 160 degrees C for > or = 2 h was insoluble in the 0.2 M acetic acid/0.1 M sodium acetate solvent. The rate and extent of the thermal reactions were increased in the presence of saturated steam; the autoclaved samples became insoluble after 2 h of heating at 115 degrees C and after 1 h at > or = 120 degrees C. On the other hand, the physical changes induced by dry heat at < or = 120 degrees C were not affected significantly by heating the chitosan samples under anoxic conditions.

Biocompatible Materials↗

Storage of partially deacetylated chitosan films.

Chitosan has wide-ranging applications as a biomaterial, but its stability in storage is not widely known. The objective of this study was to evaluate the storage stability of films prepared from chitosan of 77% deacetylation. Both the neutralized and acetate films were evaluated, as chitosan salts offer the advantage of being soluble in water at the neutral-to-basic pH range. Aqueous solutions containing 0.5-5% acetic acid were used as solvents. The X-ray diffraction pattern, the IR spectrum, water uptake, and solubility of the films were influenced by the presence of the N-acetyl functionality, the acetate ions, and storage of the films. The anhydrous chitosan crystal in the neutralized films was unstable to storage at 4 degrees C and 28 degrees C. Its formation, as well as that of the hydrated crystal, were further hindered by the presence of even small quantities of the acetate ions. The resultant amorphous nature of the acetate films, coupled with the acidifying action of the acetic acid, led to greater water uptake and solubility compared to the neutralized films. Storage reduced the differences between the neutralized and acetate films. It also minimized the influence of the initial acetic acid content on the IR absorption and water uptake of the acetate films, exerting its leveling effects mainly within the first week of storage. Using a lower storage temperature of 4 degrees C or heating the films for 2 h at 120 degrees C prior to storage did not significantly modify the results. A pertinent factor appears to be the degree of deacetylation of the chitosan that was used to prepare the films.

Anesthetics, Local↗

Preparation of a chitin-apatite composite by in situ precipitation onto porous chitin scaffolds.

Composites of chitin with calcium phosphate were obtained by in situ precipitation of the mineral from a supersaturated solution onto chitin scaffolds. The chitin scaffolds were obtained by freeze drying to give a highly porous structure possessing a polar surface favorable for apatite nucleation and growth. THe extent and arrangement of calcium phosphate deposits on the chitin and substituted chitin scaffolds were explored. Up to 55% by mass of calcium phosphate could be incorporated into chitin scaffolds. Deposits on the chitin surface were a continuous apatite carpet nature while deposits on carboxymethylated chitin surfaces displayed a spherical morphology. Carboxymethylation of chitin exerts an overall inhibitory effect towards calcium phosphate deposition, but it provides for site-specific nucleation of the mineral phase. In situ precipitation can be an important route in the future production of various polymer-calcium phosphate composites.

Apatites↗

Two-coat systems for encapsulation of spathoglottis plicata (Orchidaceae) seeds and protocorms

Complex coacervation of alginate-chitosan and alginate-gelatin were used to develop two-coat systems for the encapsulation of Spathoglottis plicata seeds and protocorms (top-shaped structures formed after seed germination of orchids). Both the seeds and the protocorms could withstand the encapsulation treatments with high viability. About 54% of seeds and 40% of large protocorms (1.6-2.0 mm) were able to tolerate a 6-h desiccation treatment. However, viability of the small protocorms (0.7-0.9 mm) was greatly reduced if they were desiccated before encapsulation. Encapsulation after desiccation significantly increased the percentage viability of seeds and protocorms. Treatment with abscisic acid (ABA, 10(-5) M) before desiccation and encapsulation resulted in high percentage viability in seeds and large protocorms whereas the small protocorms were found to be less tolerant to the treatments. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

Gamma irradiation of chitosan.

Chitosan has potential biomedical applications that may require the final products to be sterilized before use. The gamma irradiation of purified and highly deacetylated chitosan fibers and films at sterilizing doses (up to 25 kGy) caused main chain scissions. The viscosity average molecular weight of the polymer decreased with increasing irradiation dose, the radiation yields of scission being 1.16 in air and 1.53 in anoxia. Preirradiation application of a negative pressure of 100 kPa disrupted the network structure, which may have contributed to the greater radiation yield obtained by chitosan fibers in anoxia. Radiation induced scission of the chitosan chains resulted in a lower glass transition temperature (Tg), indicative of higher segmental mobility. The Tg was below ambient at an irradiation dose of 25 kGy in air. Irradiation in air improved the tensile strength of the chitosan film, probably due to changes in chain interaction and rearrangement. Irradiation in anoxia did not affect film properties significantly, partly because the preirradiation application of negative pressure had a negligible effect on the structure of the chitosan film. Polymer network structure and the irradiation conditions are therefore important determinants of the extent of radiation induced reactions in chitosan.

Biocompatible Materials↗

The influence of anionic chitin derivatives on calcium phosphate crystallization.

The influence of two water-soluble anionic chitin derivatives, sodium carboxymethyl-chitin (CM-chitin) and phosphoryl-chitin (P-chitin) on the crystallization of calcium phosphate by seeded growth and turbidimetry were studied. The adsorption of these derivatives onto hydroxyapatite obtained at 37 degrees C, fitted the Langmuir isotherm. The affinity constant and number of adsorption sites were measured at 2.9 and 1.69 micromol m(-2) for CM-chitin and 11.85 and 4.23 micromol m(-2) for P-chitin. P-chitin exerted a potent inhibitory effect on the seeded growth of hydroxyapatite from a supersaturated solution, reducing the initial rate of crystallization by more than 90% at a solution concentration of 10(-4)M. Both chitin derivatives also retarded the rate of spontaneous calcium phosphate precipitation. The type of calcium phosphate precipitated was poorly crystallized, calcium-deficient apatite. The chitin derivatives were found to be incorporated into the precipitate and influenced both the phase and morphology of calcium phosphate formed.

Anions↗

Glutaraldehyde-fixed biological tissue calcification: effectiveness of mitigation by dimethylsulphoxide.

The conditions defining the extent of dimethylsulphoxide (DMSO) effectiveness in mitigating calcification of glutaraldehyde (GA)-fixed tissue have been evaluated. Exposure of GA-fixed tissue porcine aortic valve cusps to low concentrations of DMSO does not impart calcification inhibitory activity. Mitigation in calcification becomes evident only as the DMSO component nears 100% and is best when neat DMSO is used. In all instances, regardless of the DMSO concentration, exposure to DMSO resulted in an increase in the tissue shrinkage temperature, attributed to further cross-linking in the tissue. Histological examination of samples before implantation indicate some deleterious effects to the tissue, the degree dependent on concentration, time and temperature of DMSO exposure. The results of this study suggest that treatment of GA-fixed tissue with high concentrations of DMSO for a short duration at a lowered temperature could give a bioprosthesis that has good mitigating calcification properties with retention of tissue integrity.

Journal Article↗

Hydroxyapatite modified chitin as potential hard tissue substitute material.

Calcium hydroxyapatite (HA) powder was incorporated into chitin solutions to form an intimate mixture. Upon casting of this mixture into molds of fixed dimensions with subsequent removal of solvent, HAs containing chitin flexible plates were produced. The amount of (HA) was varied from 10 to 50% by mass of HA. The elastic modulus, yield stress, and elongation to fracture, measured at a crosshead speed of 5 mm/min, of these HAs containing chitin flexible plates were evaluated. The amount of HA in the HA incorporated chitin was found to not significantly change the elastic modulus or elongation to fracture. However, a decrease in the maximum tensile stress with an increase in the HA content was found.

Biocompatible Materials↗

Methods for the treatment of collagenous tissues for bioprostheses.

Collagenous tissue as a biomaterial possesses many favourable characteristics and advantages over synthetic materials. The resemblance to human tissue suggests that it has a performance advantage over alternative materials. This advantage has been exploited to produce clinical devices that have been implanted in patients for more than a quarter of a century. The method of treating collagenous tissue for bioprostheses has developed from crude exposure of tissue to chemicals to a sophisticated level of considering the biochemical, chemical, engineering and clinical aspects of the process. This review focuses on the various chemical and physical treatments that have made the bioprostheses possible, highlighting the chemical agents and the cross-linking mechanism involved.

Animals↗