Argyrios Margaritis

Microbial Biosynthesis of Polyglutamic Acid Biopolymer and Applications in the Biopharmaceutical, Biomedical and Food Industries

ABSTRACT This review article provides an updated critical literature review on the production and applications of Polyglutamic Acid (PGA). α-PGA is synthesized chemically, whereas γ-PGA can be produced by a number of microbial species, most prominently various Bacilli. Great insight into the microbial formation of γ-PGA has been gained thanks to the development of molecular biological techniques. Moreover, there is a great variety of applications for both isoforms of PGA, many of which have not been discovered until recently. These applications include: wastewater treatment, food products, drug delivery, medical adhesives, vaccines, PGA nanoparticles for on-site drug release in cancer chemotherapy, and tissue engineering.

A MODIFIED LANGMUIR MODEL FOR THE PREDICTION OF THE EFFECTS OF IONIC STRENGTH ON THE EQUILIBRIUM CHARACTERISTICS OF PROTEIN ADSORPTION ONTO ION EXCHANGE/AFFINITY ADSORBENTS

Abstract An empirical model modified from the Langmuir isotherm model to account for the effects of ionic strength on the equilibrium characteristics of protein adsorption onto ion exchange/affinity adsorbents has been proposed and tested against experimental and literature data. The equilibrium isotherms for BSA adsorption onto a polystyrenic anion exchanger, Diaion HPA25, were established for five different NaCl concentrations at 25°C, pH 7.0. The apparent Langmuir parameters in the new model (qm′ and Kd′), which replace the Langmuir parameters (qm and Kd) in the original Langmuir model, were determined by non-linear curve fitting. The proposed model has been shown to be applicable to various protein/adsorbent systems.

Advances in Ethanol Production using Immobilized Cell Systems

The application of immobilized cell systems for the production of ethanol has resulted in substantial improvements in the efficiency of the process when compared to the traditional free cell system. In this review, the various methods of cell immobilization employed in ethanol production systems have been described in detail. Their salient features, performance characteristics, advantages and limitations have been critically assessed. More recently, these immobilized cell systems have also been employed for the production of ethanol from non-conventional feedstocks such as Jerusalem artichoke extracts, cheese whey, cellulose, cellobiose and xylose. Ethanol production by immobilized yeast and bacterial cells has been attempted in various bioreactor types. Although most of these studies have been carried out using laboratory scale prototype bioreactors, it appears that only fluidized bed, horizontally packed bed bioreactors and tower fermenters may find application on scale-up. Several studies have indicated that upon immobilization, yeast cells performing ethanol fermentation exhibit more favourable physiological and metabolic properties. This, in addition to substantial improvements in ethanol productivities by immobilized cell systems, is indicative of the fact that future developments in the production of ethanol and alcoholic beverages will be directed towards the use of immobilized cell systems. 291 references.

Bioprocess Developments in the Production of Bioinsecticides by Bacillus Thuringiensis

Perspectives technologiques de la lutte contre les insectes. Aspects economiques. Applications sur le terrain. Caracteristiques generales. Parametres de fermentation. Besoins concernant la formulation. Procedes commerciaux de production

Poly(glutamic acid) for biomedical applications.

ABSTRACT:  Paclitaxel is a widely used anti-cancer agent. Conjugates of paclitaxel with poly(glutamic acid) have shown great promise in preclinical trials, and clinical trials are now underway. Preclinical data suggest that more paclitaxel is preferentially delivered to tumor sites vs. nonconjugated paclitaxel. When poly(glutamic acid) is conjugated to other families of cancer drugs, similar improvements in effectiveness and reduced toxicity are observed. Optimization of poly(glutamic acid) for use in drug delivery applications is a key step in making this technology viable.

Controlled release of doxorubicin from doxorubicin/γ-polyglutamic acid ionic complex

Formation of drug/polymer complexes through ionic interactions has proven to be very effective for the controlled release of drugs. The stability of such drug/polymer ionic complexes can be greatly influenced by solution pH and ionic strength. The aim of the current work was to evaluate the potential of γ-polyglutamic acid (γ-PGA) as a carrier for the anticancer drug, Doxorubicin (DOX). We investigated the formation of ionic complexes between γ-PGA and DOX using scanning electron microscopy, spectroscopy, thermal analysis, and X-ray diffraction. Our studies demonstrate that DOX specifically interacts with γ-PGA forming random colloidal aggregates and results in almost 100% complexation efficiency. In vitro drug release studies illustrated that these complexes were relatively stable at neutral pH but dissociates slowly under acidic pH environments, facilitating a pH-triggered release of DOX from the complex. Hydrolytic degradation of γ-PGA and DOX/γ-PGA complex was also evaluated in physiological buffer. In conclusion, these studies clearly showed the feasibility of γ-PGA to associate cationic drug such as DOX and that is may serve as a new drug carrier for the controlled release of DOX in malignant tissues.

The effects of high field DC pulse and liquid medium conductivity on survivability of Lactobacillus brevis

Survivability of Lactobacillus brevis cells in suspensions of phosphate buffer solutions of different conductivities (170 μS/cm to 2230 μS/cm) using electric pulse application has been investigated under varied test conditions. Survivability decreased rapidly with the application of the first few pulses (approx. 25 to 50 depending on the test conditions). However, the destruction performance decreased with increased number of pulse applications. Hence to obtain a maximum reduction in survivability, the electrical conditions should be so selected that effective killing is achieved with the fewest number of pulses applied. The maximum reduction in survivability (N/N0, approx. 10−7) was obtained in liquid possessing the lowest conductivity (170 μS/cm) with an application of 150 pulses of 160-μs pulse width. Despite the increase in liquid medium temperature during pulse treatment, the killing was significantly due to pulse as the maximum temperature rise (22° C) during treatment was insufficient to cause any synergistic effect of temperature and pulse treatment. In this work we have shown for the first time that if the pulse width is kept constant, the higher reduction in survivabilities observed in liquids with lower conductivities was primarily due to conductivity influencing the membrane permeability. The small change in test liquid pH (<0.5) indicated that the killing of cells was affected primarily by high field pulses rather than by-products of electrolysis in the medium of different conductivities.

High ethanol productivities using small Ca-alginate beads of immobilized cells of Zymomonas mobilis

SummaryZymomonas mobilis cells were immobilized into small 1 mm diameter beads of Ca-alginate in order to minimize mass transfer limitations and maximize immobilized cell activity. A combination of small bead size with a high cell concentration of 58 g dry wt. cell per lit. bead volume resulted in high ethanol productivities using a newly designed packed bed bioreactor system. Steady-state dilution rates ranging from 0.4 h-1 to 3.9 h-1 were run resulting in a maximum productivity of 102 g ethanol/l/h for an inlet substrate concentration of 100 g glu/l and 87% conversion. The bioreactor was run continuously at a fixed dilution rate for 384 h and short intermittent treatment of the beads with CaCl2 temporarily increased ethanol productivity to a maximum of 116 g ethanol/l/h.

The effects of non-Newtonian fermentation broth viscosity and small bubble segregation on oxygen mass transfer in gas-lift bioreactors: a critical review

Abstract This review paper deals with the effects of non-Newtonian fermentation broth viscosities on gas–liquid mixing and oxygen mass transfer characteristics to provide knowledge for the design and development of gas-lift bioreactors, which can operate satisfactorily with high viscosity fermentation broths. The effect of small bubble segregation is also examined.

Production and Characterization of γ-Polyglutamic Acid Nanoparticles for Controlled Anticancer Drug Release

γ-Polyglutamic acid (γ-PGA) is a hydrophilic, biodegradable, and naturally available biopolymer produced by a number of microbial species, most commonly, the Bacillaceae family. Its biological properties such as nontoxicity, biocompatibility, and nonimmunogenicity qualify it as an important biomaterial in drug delivery applications. This review focuses mainly on the development of γ-PGA nanoparticles as drug delivery carriers for anticancer therapeutics. We discuss various techniques for the production and characterization of γ-PGA nanoparticles and controlled-release strategies. We also present a brief overview of the tumor physiology that forms the basis for the development of various targeted drug delivery approaches in cancer chemotherapy.