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Biomedical subjects

N Lotan

Publications and source records attributed to N Lotan.

At least 19 recordsLinked to original sources
PubMed1999

Microparticles of novel branched copolymers of lactic acid and amino acids: preparation and characterization.

The preparation and characterization of microparticles produced from a new class of functionalized, biodegradable, comblike graft copolymers is presented. The copolymers are polyester-polyamino acid hybrids, composed of a poly(L-lactic acid-co-L-lysine) (PLAL) backbone, and poly(L-lysine), poly(D,L-alanine) or poly(L-aspartic acid) side chains extending from the lysine residues of PLAL. The microparticles have been characterized with regard to their surface properties, morphology, and size. Thus, electron spectroscopy for chemical analysis data and results of Zeta potential measurements suggest that the polyamino acid side chains tend to concentrate at the surface of the particles. Also, analyses by environmental scanning electron microscopy and confocal scanning laser microscopy indicate that particles carrying poly(lysine) chains have an unusual porous structure, most probably due to the combined effects of the amphiphilic, polyelectrolyte, and chemical nature of the composing copolymer, as well as of the particular preparation technique employed. The capabilities of the microparticles to serve as carriers in controlled drug release and delivery devices were demonstrated by encapsulation and release of rhodamine B, a low molecular weight drug model.

Aerosols↗
PubMed1999

Dual enzyme multi-layer bioreactors: analytical modeling and experimental studies.

Enzymic reactors are developed for a variety of biomedical-biotechnological applications, including blood detoxification. For the latter, an appropriate approach is to use enzymes of the Mercapturic Acid Pathway. The first two enzymes of this pathway are Glutathione-S-Transferase (GST) and gamma-Glutamyl Transpeptidase (gamma GT). Earlier, the performance of an immobilized GST reactor was investigated experimentally and theoretically. Here, the analytical model was extended to describe a dual-enzyme continuous packed-bed reactor (DCP), in which the two enzymes (E1 and E2) are arranged in alternating layers. The performance of DCP reactors was first studied by numerical simulations, considering the effects of reactor configuration (i.e. number of enzyme layers), kinetic characteristics (K(m), Vmax, Kiq) and operational parameters (flow rate, substrates concentration). Results were obtained in terms of substrate and products concentration profiles along the reactor. The theoretical calculation were supplemented by experimental studies. In the latter GST (i.e. E1) and gamma GT (i.e. E2), were used when immobilized on porous beads, and the reactor was set up and operated in various configurations. It was found that the factors which mostly affect the performance of DCP systems are reactor configuration and extent of inhibition of E1 by its reaction product.

Animals↗
PubMed1997

Large porous particles for pulmonary drug delivery.

A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.

Administration, Inhalation↗
PubMed1997

Nanotechnology for biomaterials engineering: structural characterization of amphiphilic polymeric nanoparticles by 1H NMR spectroscopy.

Nanoparticles composed of diblock poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) or a branched, multiblock PLA-(PEG)3 were prepared by the single emulsion technique. Results of previous studies of these nanoparticles suggested that their structure is of the core-corona type with a polyester core and an outer PEG coating. In the present study, 1H NMR spectroscopy was utilized to provide direct evidence of the structure of these nanoparticles suspended in an aqueous environment. The results confirm the existence of the core-corona structure under these conditions, and show that the PEG moieties extend out from the nanoparticle core into the aqueous environment, and exhibit chain mobility similar to that of PEG in solution.

Biocompatible Materials↗
PubMed1997

A molecular switch for biochemical logic gates: conformational studies.

This report presents the computer-assisted design of a molecular switching element, in which a molecular switch regulates the enzymatic activity of Ribonuclease A (RNase A). The molecular switch, an appropriately modified amino acid residue, is constructed with an electron donor group and an electron acceptor group, connected to one another with a conjugated double bond bridge. The switching mechanism is based on the azonium-hydrazo tautomerization, by which a charge separation induced in the excited state causes a rearrangement of the molecular electronic structure, resulting in the exchange of locations of single and double bonds. This rearrangement of bonds leads to different three-dimensional conformations of the switch. Using the electrostatically driven Monte Carlo (EDMC) method and the empirical conformational energy program for peptides (ECEPP/3) potential energy function, we carried out an exhaustive search of the conformational space of the switching element. The results of these calculations reveal two sets of conformations: in one set the access to the active site of the enzyme is preferentially blocked, while in the other set the active site is preferentially accessible. Integration of the designed element into biochemical logic gates operating under the rules of threshold value, and experimental implementation of this system, are considered.

Protein Conformation↗
PubMed1986

Enzyme-based hemoperfusion and blood treatment.

Enzyme-based artificial organs are being developed as metabolic assist devices. These are required when normal metabolism is impaired, or when the body is overloaded by undesired metabolites or toxins. The implementations of this approach for treating a genetic disease, and for metabolic support in liver failure are envisaged. The kinetic aspects and mass transfer characteristics of bioreactors for these systems are considered in detail.

Blood↗
PubMed1984

Tailor-made agarose-based reactive beads for hemoperfusion and plasma perfusion.

Composite beads of approximately 1 mm diameter, made of crosslinked agarose and containing Fuller's Earth or zirconium oxide powders, were prepared and used in extracorporeal systems for blood detoxification. The former was used for the removal of Paraquat, while the latter was used to remove inorganic phosphate from hyperphosphatemic animals with or without acute renal failure. The high surface area of the powder, combined with the low resistance to diffusion in the crosslinked agarose matrix, are highly advantageous. The crosslinking provides high mechanical strength, heat stability, prolonged shelf life, good blood flow characteristics, and prevents the release of fine particles into the blood. Crosslinked agarose beads of 1 mm diameter, containing chemically-bound heparin were also prepared, and used as a model for direct contact removal of LDL-cholesterol from the blood of familial hypercholesterolemic patients by hemoperfusion. The high capacity of these beads (over 5 mg LDL/mL beads) indicates that this clinical modality can replace the highly expensive plasmapheresis procedure presently used.

Animals↗
PubMed1983

Novel composite sorbent beads for paraquat removal by hemoperfusion.

The present report describes the development and performance of a column that is to be used for removal of paraquat from circulating blood in a hemoperfusion-type set-up. The key element of the system is a newly developed sorbent material containing fuller's earth entrapped in cross-linked agarose beads (Talosit). The technique produces a sorbent material exhibiting a very large active surface area while allowing for high mobility of paraquat molecules within the beads and favorable flow characteristics of packed column. Cross-linking of the agarose (by epichlorohydrin) also has a most beneficial effect on the mechanical strength of the beads as well as on their stability to sterilization in an autoclave. The composite beads exhibit good blood compatibility. A scanning electron microscope analysis of the beads showed no adherence of cellular blood components after contact with blood. Moreover, no significant changes in plasma composition had taken place when the beads were properly conditioned prior to contact with fresh human blood. A comparative study of paraquat removal from saline solution by the new beads and by cellulose-coated activated charcoal (Adsorba-300C) indicates a higher removal rate with the former. The results obtained so far with this new sorbent are very promising and extension of these studies to in vivo hemoperfusion is under way.

Adsorption↗
PubMed1983

In vivo evaluation of a composite sorbent for the treatment of paraquat intoxication by hemoperfusion.

In vivo evaluation of a new hemoperfusion (HP) device for Paraquat detoxification is reported. The key element of the extracorporeal system is a column packed with newly developed composite sorbent beads containing Fullers' Earth (FE) entrapped in crosslinked Agarose. The proposed HP system exhibits very good biocompatibility characteristics when conventional heparinization is supplemented by infusing 0.02 ml per min acid-citrate dextrose (ACD) solution per ml. perfused blood at the inlet to the HP column. No complications or abnormalities were detected in animals which were hemoperfused with the system described. It is suggested that the new device is effective and safe for clinical application.

Aluminum Compounds↗