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N Angelova

Publications and source records attributed to N Angelova.

9 recordsLinked to original sources

Permeability and stability of chitosan-based capsules: effect of preparation.

Capsules were obtained by interpolymer complexation between chitosan (polycation) and sodium hexametaphosphate (oligoanion). The effect of preparation variables such as the pH, ionic strength as well as the reagent and porogen concentration on the capsule characteristics was evaluated. By decreasing the chitosan/SMP ratio, adding mannitol up to 1% or maintaining the salt concentrations below 0.15 w/v%, the diffusion characteristics can be modulated without disturbing the capsule mechanical stability. Higher concentrations of the cross-linking agent (2.25 w/v%) produced stable capsules only in the absence of electrolyte and low polyol amounts. Furthermore, by increasing the ionic strength, or the pH of the initial chitosan solution, the membrane exclusion limit shifted to higher values concomitant with a significant loss in the membrane compression resistance. The results obtained showed that the capsule characteristics could be independently controlled by manipulating the coacervation conditions.

Capsules↗

Maintenance of primary murine hepatocyte functions in multicomponent polymer capsules--in vitro cryopreservation studies.

BACKGROUND/AIMS: The potential of a new encapsulation system has been evaluated as an artificial housing for liver cells. METHODS: Murine hepatocytes were encapsulated in specially designed multicomponent capsules formed by polyelectrolyte complexation of sodium alginate, cellulose sulphate and poly(methylene-co-guanidine) hydrochloride, the permeability of which has previously been characterised. RESULTS: We demonstrate here the absence of cytotoxicity and the excellent biocompatibility of these capsules towards primary culture of murine hepatocytes. Experimental results demonstrated that the encapsulated hepatocytes retained their specific functions--transaminase activity, urea synthesis and protein secretion--over the first 4 days of culture in minimum medium. The cryopreservation of encapsulated hepatocytes, for periods of up to 4 months, did not alter their functional capacities, as no major differences were observed between unfrozen and frozen encapsulated cells for the functions tested. CONCLUSIONS: Because of the absence of cytotoxicity, and the ease of handling and cryopreservation, while maintaining liver specific functions, the described system appears to be valuable for murine liver cell encapsulation. It is also a promising tool for fundamental research into drug metabolism, intercellular regulation, metabolic pathways, and the establishment of banks for the supply and storage of murine hepatocytes.

Animals↗

Development of a coculture model of encapsulated cells.

In the whole animal, metabolic regulations are set by reciprocal interactions between various organs, via the blood circulation. At present, analyses of such interactions require numerous and uneasily controlled in vivo experiments. In a search for an alternative to in vivo experiments, our work aims at developing a coculture system in which different cell types are isolated in polymer capsules and grown in a common environment. The signals exchanged between cells from various origins are, thus, reproducing the in vivo intertissular communications. With this perspective, we evaluated a new encapsulation system as an artificial housing for liver cells on the one hand and adipocytes on the other hand. Murine hepatocytes were encapsulated with specially designed multicomponent capsules formed by polyelectrolyte complexation between sodium alginate, cellulose sulphate and poly(methylene-coguanidine) hydrochloride, of which the permeability has been characterized. We demonstrated the absence of cytotoxicity and the excellent biocompatibility of these capsules towards primary culture of murine hepatocytes. Encapsulated hepatocytes retain their specific functions--transaminase activity, urea synthesis, and protein secretion--during the first four days of culture in minimum medium. Mature adipocytes, isolated from mouse epidydimal fat, were embedded in alginate beads. Measurement of protein secretion shows an identical profile between free and embedded adipocytes. We finally assessed the properties of encapsulated hepatocytes, cryopreserved over a periods of up to four months. The perspective of using encapsulated cells in coculture are discussed, since this system may represent a promising tool for fundamental research, such as analyses of drug metabolism, intercellular regulations, and metabolic pathways, as well as for the establishment of a tissue bank for storage and supply of murine hepatocytes.

Adipocytes↗

Objectively assessing bioartificial organs.

The metrics used, thus far, to assess bioartificial organ function are shown to be subjective and requiring validation. Therefore, four categories of correlations are proposed based on, respectively, device, in vitro and in vivo evaluations, and clinical function. Examples are presented whereby the correlations among individual indicators are used as a means to expedite the development of immunoisolated cells. Specifically, a case study illustrating the validation of in vitro indicators of in vivo graft function for the bioartificial pancreas (microencapsulated islets) is summarized. This has revealed thresholds with respect to given metrics relating to in vivo device function, the necessity to couple bioartificial organ design with transplant site selection, as well as the lack of objectivity involved in the evaluation and establishment of hypotheses. Specific quantitative indicators illustrate the need for quality-controlled measures, for example, relating to the tolerance of microcapsule diameter and membrane thickness distributions. Qualitative indices representing fibrosis and device properties (e.g., sphericity) are also used to describe the need for in vitro experiments in the development of bioartificial organs.

Bioartificial Organs↗

Stability assessment of chitosan-sodium hexametaphosphate capsules.

The assessment of the stability of capsules based on chitosan-sodium hexametaphosphate complex formation has been carried out using two independent methods--compression and osmotic swelling, and the influence of the preparation variables was evaluated. The formulation containing 1.5% core polymer (chitosan) and 1.5% oligophosphate, in the absence of salt or at low ionic strength (0.15% NaCl) was found to provide the best membrane resistance. A higher concentration of cross-linker (2.25%) produced stable capsules only in absence of electrolyte. Mannitol, a porogen added to the preparation solutions, did not affect the stability of the obtained membranes. At elevated polyol (1%) and cross-linker levels (2.25%), and at 0% salt, membranes with decreased elasticity were obtained, having lower compression and osmotic bursting values and lower deformation at the breaking points. A significant influence of salt amount on the capsule stability was also found. This was attributed to changes in the membrane formation process resulting in membranes with different thickness and structure. Membrane compression stability was found to be dependent on the pH of both oligophosphate and chitosan solutions, as well as on the reaction time. The bursting force values decreased for capsule diameters below 1.6 mm. The increased membrane/capsule volume ratio for the small capsules decreased the capsule deformation freedom and caused capsule rupture at low force values. The capsules made at low salt amounts showed very good storage stability over time and at elevated temperatures. The results demonstrated that the capsules could be formulated with controlled properties for various biomedical applications.

Capsules↗

Effect of preparation conditions on properties and permeability of chitosan-sodium hexametaphosphate capsules.

Capsules were obtained by interpolymer complexation between chitosan (polycation) and sodium hexametaphosphate (SMP, oligoanion). The effect of the preparation conditions on the capsule characteristics was evaluated. Specifically, the influence of variables such as pH, ionic strength, reagent concentration, and additives on the capsule permeability properties was investigated using dextran as a model permeant. The capsule membrane permeability was found to increase by decreasing the chitosan/SMP ratio as well as adding mannitol to the oligoanion recipient bath. Increasing the ionic strength or the pH of the initial chitosan solution was also found to enhance the membrane permeability, moving the membrane exclusion limit to higher values. Generally, the capsules prepared tinder all tested conditions had a relatively low permeability which rarely exceeded a molecular cut-off of 40 kD based on dextran standards. Furthermore, the diffusion rate showed a strong temporal dependence, indicating that the capsules prepared under various conditions exhibit different apparent pore size densities on the surface. The results indicated that, in order to obtain the desired capsule mass-transfer properties, the preparation conditions should be carefully considered and adjusted. Adding a polyol as well as low salt amount (less than 0.15%) is preferable as a means of modulating the diffusion characteristics, without disturbing the capsule mechanical stability.

Capsules↗

Rationalizing the design of polymeric biomaterials.

Polymers are a promising class of biomaterials that can be engineered to meet specific end-use requirements. They can be selected according to key 'device' characteristics such as mechanical resistance, degradability, permeability, solubility and transparency, but the currently available polymers need to be improved by altering their surface and bulk properties. The design of macromolecules must therefore be carefully tailored in order to provide the combination of chemical, interfacial, mechanical and biological functions necessary for the manufacture of new and improved biomaterials.

Animals↗

[Antithrombin III and its role in normal and pathological hemostasis].

The paper is a survey on the latest up-to-date data on the character, determination methods, physiology, pathophysiology and clinical significance of one of most important factors of anticoagulation system--antithrombin III. Its normal activity is of essential importance for physiological hemostasis. It could be reduced via diminished production, increased elimination and intensified consumption, particularly in case of concomitant grave states and diseases. The enhanced activity of antithrombin III, found most frequently in the treatment with indirect anticoagulants, renal transplantations, and application of anabolic steroids, has given no data of clinical importance so far. Numerous of the outlined problems remain still not sufficiently elucidated.

Antithrombin III↗