Surface and swelling properties of mucoadhesive blends and their ability to release fluconazole in a mucin environment.

The aim of this study is to characterize the matrices for the controlled release of fluconazole and to expand the knowledge of their physicochemical properties that influence the process of mucoadhesion. Polymeric carriers of fluconazole were prepared using the following mucoadhesive polymers: Carbopol 974 P NF, Noveon AA-1, HPMC, HEC, chitosan and film-forming polymer Kollidon VA 64. The potential mucoadhesive properties of the polymers and their blends were evaluated by measuring the wettability and then calculating the surface free energy defined by OWRK and vOCG models, determining the polar and dispersion forces, spreading coefficients and work of adhesion of polymers and their blends with fluconazole in the form of tablets. Prepared tablets were characterized by swelling capacity and in vitro drug release to estimate the amount of fluconazole release from selected polymer blends. The study of drug release from selected blends both in simulated saliva fluid (pH = 6.8) and in simulated vaginal fluid (pH = 4.2) containing mucin confirmed the ability of polymeric carriers to continuously deliver drug over a period of about 8 h.

Surface properties and surface free energy of cellulosic etc mucoadhesive polymers.

The paper presents the sorption and wettability properties for several mucoadhesive polymers (Carbopol 974P NF (carbomer polymer; carboxy polymethylene), Noveon AA-1, (polycarbophil; acrylic acid polymer crosslinked with divinyl glycol) HPMC (hypromellose; cellulose 2-hydroxyethyl methyl ester) and HEC (cellulose 2-hydroxyethyl ether) and a film-forming polymer Kollidon VA 64 (polyvinylpyrrolidone-vinyl acetate copolymer)) commonly used in controlled drug delivery systems. Moreover, the surface energy of powders was determined using the data obtained according to the three types of experimental investigation. The contact angle measurements for powders were performed according to the Washburn method and using the capillary rise technique. Whereas the sessile drop method was performed on the compressed discs of mucoadhesive polymers. For the surface characterization the IGC technique was also applied. The results obtained by different methods, for both: wettability and surface energies, were compared and correlated. The presented study showed significant differences in the morphology and surface properties of mucoadhesion polymers considered. It was confirmed that for the accurate quantification of the free surface energy (and its components), for mucoadhesive polymers considered, not only the IGC in finite concentration, but also the Washburn method should be used.

The wettability and swelling of selected mucoadhesive polymers in simulated saliva and vaginal fluids.

The surface properties play a particularly important role in the mucoadhesive drug delivery systems. In these formulations, the adsorption of polymer matrix to mucous membrane is limited by the wetting and swelling process of the polymer structure. Hence, the performance of mucoadhesive drug delivery systems made of polymeric materials depends on multiple factors, such as contact angle, surface free energy and water absorption rate. The aim of our study was to analyze the effect of model saliva and vaginal fluids on the wetting properties of selected mucoadhesive (Carbopol 974P NF, Noveon AA-1, HEC) and film-forming (Kollidon VA 64) polymers as well as their blends at the weight ratio 1:1 and 1:1:1, prepared in the form of discs. Surface properties of the discs were determined by measurements of advancing contact angle on the surface of polymers and their blends using the sessile drop method. The surface energy was determined by the OWRK method. Additionally, the mass swelling factor and hydration percentage of examined polymers and their blends in simulated biological fluids were evaluated.

[Microencapsulated multicellular tumor spheroids: preparation and use as a novel in vitro model for drug screening].

In the current study a technique for microencapsulation of human breast adenocarcinoma cells MCF-7 in alginate-chitosan microcapsules is used. Microencapsulation is proposed to generate multicellular tumor spheroids (MTS) based on these cells and to test them further as an in vitro model for anti-tumor drug screening. Cytotoxicity of methotrexate (MTX) was studied on the obtained MTS. A set of MTS with mean size of 150, 200 and 300 m was prepared in function of a cultivation time. After incubation of MTS in cultivation medium containing MTX at concentrations of 1, 2, 10, 50 and 100 nM for 48 hs cell viability was evaluated. MTS were shown to be more resistant to MTX than the monolayer culture, and the resistance to MTX was increased with enhancing a spheroid size. At MTX concentration of 100 nM a number of viable cells in MTS with the size of 300 m was 2.5-fold bigger than that one in monolayer culture. It is suggested that the cells in microencapsulated MTS can better mimic cell behavior in a small size solid tumor than the cells in a monolayer culture. In future microencapsulated MTS can be proposed as a novel in vitro model for anticancer drug screening.

[Alginate-chitosan microspheres for the specific sorption of antibodies].

Potentially hemocompatible alginate-chitiosan microparticles and microcapsules coated with a semipermeable membrane with incorporated glycoconjugates were synthesized. The membrane acts as a barrier, which keeps the incorporated glycoconjugate from going outside but permits antibodies to penetrate inside and specifically bind to antigens, high-molecular polysaccharide conjugates. The carriers obtained are highly competitive in sorption capacity with Sepharose modified by the same oligosaccharides.

Biocompatible oligochitosans as cationic modifiers of alginate/Ca microcapsules.

In the past, it has been proven that by properly adjusting the molecular mass of the oligochitosan samples, it is possible to optimize the formation of rigid, biocompatible capsules with semipermeable membranes under physiological conditions. In this study, the feasibility of four oligochitosan samples, with varying molar masses (M(n) in range 3-5 kDa), as biocompatible coatings of alginate/Ca capsules was investigated. By selection of appropriate depolymerization and purification methods we obtained oligochitosan samples that appeared to be noncytotoxic for C(2)C(12) myoblasts and did not influence the mammalian cell metabolism especially in relative short time during the process of capsule formation. Furthermore, oligochitosans can be used as a tool to reduce the membrane cut-off of the alginate capsules. However, such reduction, as well as mechanical resistance of formed microcapsules, depend on MM of the cationic polysaccharide and the chemical composition of the alginate (mannuronic/guluronic acid ratio). Here, we address that the use of low molar mass chitosan (< 5000 g/mol) permits the formation of mechanical stable capsules at physiological pH, which represents a strong advantage over other chitosan-based chemistries.

Carrageenan-oligochitosan microcapsules: optimization of the formation process(1).

The formation of new microcapsules based on polyelectrolyte complexes between carrageenans and oligochitosan has been investigated. The optimization of the process, which includes the selection of the most suitable solvent and investigation of the influence of reaction conditions on capsule properties, is presented. Iota-carrageenan (1.2-2% wt.) prepared in HEPES buffer was found to be the most suitable for the formation of mechanically stable capsules. These new capsules combine extremely high deformability (>90%) and elasticity with permeability control and can be applied in various bioencapsulation technologies. It has been shown that the reaction time influences the mechanical properties, whereas carrageenan concentration and the temperature during the capsule formation effect both mechanical and porosity characteristic of the membrane. Moreover, the temperature influences the kinetics of the diffusion through the complex iota-carrageenan/oligochitosan membrane. In general egress is faster above the sol-gel transition point, indicating applicability in thermo-induced releasing systems.

Optimal conditions of transplantable binary polyelectrolyte microcapsules.

Binary polyanion/oligocation microcapsules, prepared in a one-step process, are proposed as an alternative to the common alginate/poly-L-lysine system used in bioencapsulation technology. The model system is based on natural polysaccharides and involves the anionic sodium alginate, or iota-carrageenan, complexed with cationic oligochitosan. This system has been characterized with respect to capsule formation, mechanical strength, and permeability. This paper provides a general description of the influence of the most pronounced parameters that can be used as a tool to modulate the properties of binary microcapsules. These parameters have been separated into two categories. The first, which includes molar mass of polyanion, pH, ionic strength, and concentration of both polyelectrolytes, can be used to simultaneously control capsule mechanical and structural properties. The second set, molar mass of polyanion and reaction time, influences only mechanical resistance without altering membrane permeability. Additional issues related to mechanical stability and the possible change of capsule properties following transplantation are discussed.

Physical and mechanical behavior of electron-beam irradiated and ethylene oxide sterilized multiblock polyester.

The effect of two sterilization treatments (electron-beam radiation and ethylene oxide gas) on the structure and mechanical properties of a multiblock copolymer were investigated to establish the effects of the sterilizing procedures on potential biomedical material. The material was exposed for different radiation doses in order to find an optimum dose of electron-beam radiation. Characterization techniques employed include gel permeation chromatography, infrared spectroscopy, differential scanning calorimetry, dynamic mechanical thermal analysis and tensile testing. The optimal dose of radiation at which no change in structure and mechanical properties occurred was found as 25 kGy. Ethylene oxide gas treatment also did not affect the structure and properties of the polymer and it can be recommended as an alternative sterilization route for the studied polymer.

New microcapsules based on oligoelectrolyte complexation.

A new one-step microencapsulation procedure has been developed. For the alginate/oligochitosan system the molar mass of the chitosan is a key parameter in the formation of stable, elastic capsules with high modulus. Furthermore, the selection of an optimum molar mass provides an additional degree of freedom, permitting the simultaneous regulation of mechanical properties and permeability without the need for multicomponent organic-inorganic chemistries as have been previously employed. The effects of molar mass of chitosan, its concentration, the alginate molar mass and its metal salt on the preparation, physical properties, and release characteristics of the capsules have been studied.

New multicomponent capsules for immunoisolation.

A new generation of microcapsules based on the use of oligomers which participate in polyelectrolyte complexation reactions has been developed. These freeze-thaw stable capsules have been applied as a bioartificial pancreas and have resulted in normoglycemia for periods of six months in concordant xenotransplantations. The new chemistry permits the control of permeability and mechanical properties over a wide range and can be adapted both to microcapsule and hollow fiber geometries rendering it a robust tool for encapsulation in general. Methods, and metrics, for the characterization of the mechanical properties and permeability of microcapsules are presented.

[Effect of superoxide dismutase on the number of chromosome aberrations in lymphocytes after irradiation of human blood preparations]. / Wplyw dysmutazy ponadtlenkowej na wydajnosc aberracji chromosomowych limfocytów po napromieniowaniu preparatów krwi ludzkiej.

The aim of the present study was to determine the radioprotective effects of endo- and exogenous SOD on the number of post-radiation chromosomal aberrations in human lymphocytes from irradiated samples of whole blood. Blood samples from 17 donors were irradiated with the dose of 1 Gy of neutron radiation or with 2 Gy of gamma radiation. Specific endogenous activity of SOD was assessed in lymphocytes from both irradiated and non-irradiated blood samples. Lymphocytes were then cultured in standard conditions with the application of PHA as a stimulator of cell divisions. The rate of chromosomal aberrations was determined in lymphocytes obtained from these cultures. Preliminary results revealed relatively low SOD activity in lymphocytes from normal (non-irradiated) blood samples, though it could vary among individuals from 1.19 to 8.81 U/mg of protein (in extreme cases the differences are even eight-fold). In further experiments, however, no relationship between the level of endogenous SOD activity and number of postradiation chromosomal aberrations was found (exposure of blood samples to the dose of 1 Gy of neutron high LET radiation.

Aging of the erythrocyte. XIX. Decrease in surface charge density of bovine erythrocytes.

Decrease in electrophoretic mobility of erythrocytes, increase in Km of erythrocyte membrane acetylcholinesterase and decrease in the binding constant of 8-anilino-1-naphthalene sulfonate to erythrocyte membranes demonstrate a decrease in surface charge density of bovine erythrocytes during in vivo aging. This phenomenon seems to be species-specific; it may be due to a diminution of the sialic acid content but may also be contributed by conformational changes of membrane proteins.

Aging of the erythrocyte. XVIII. Changes in kinetic properties of acetylcholinesterase.

Comparison of kinetic properties of acetylcholinesterase in membrane preparations from various density (age) fractions of bovine erythrocytes revealed in increase in Km value, ascribed to decrease in membrane surface potential, with increasing cell age. Activation energy of the enzyme decreased during red cell aging.