Carlos M. Corvalan

A multi-scale stochastic drug release model for polymer-coated targeted drug delivery systems.

A multi-scale mathematical model for drug release of oral targeted drug delivery systems was developed and applied to a commercially available delayed release tablet (Asacol) that delivers 5-aminosalicyclic acid (5-ASA) to the colon. Underlying physical and biochemical principles governing the involved processes (diffusion and dissolution) were employed to develop the mathematical description. Finite element formulation was used to numerically solve the model equations. Molecular dynamics (MD) simulations were used to predict macro-scale transport properties of the drug and the biologic fluid. The effect of pH variability in the gastrointestinal tract environment on the dissolution of the polymeric enteric coating was investigated using the Monte Carlo method. The direct coupling method employed (MD) predicted a sufficiently accurate diffusion coefficient (5.7x10(-6) cm2 s-1) of the drug molecules in reasonable (3 h) computation times. The model was validated using experimental data from in vitro dissolution experiments and provided accurate prediction of the drug release from the delivery system (root mean square error of 5%). The amount of drug entering the systemic circulation, computed from the predicted drug release in varying pH environments in the small bowel, was 15-24%. This range was in good agreement with clinical in vivo data (13-36%) obtained from literature. This research shows that in silico experiments using mechanistic models and stochastic approaches can be used for drug design and optimization and as a decision making tool for physicians.

A model describing the two-dimensional calendering of finite width sheets

Abstract A model that describes the two-dimensional flow of power-law fluids during calendering of finite sheets is presented. Unlike the one-dimensional calendering model in which the sidewise flow is neglected, the model presented in this work takes into account both lengthwise and sidewise flow. The lubrication approximations are used to simplify the equations of motion. The model is characterized by a free moving boundary at the sheet side edge. This free moving boundary was determined by assuming a zero velocity component for the sheet in the direction normal to the sheet side edge. This condition allows one to locate the position of the sheet side edge and thus to describe the sheet shape. The partial differential equations describing the model were solved by using the finite element method. Results obtained from the model showed that the sidewise flow, and the pressure field are a function of the system dimensions such as roll radius ( R ), gap between rolls ( H 0 ), sheet initial width and thickness ( W 0 and H F , respectively) and the rheology of the material. Results were expressed by a dimensionless parameter, named sheet spread and defined as the ratio between the final and initial width of the sheet ( W / W 0 ), which is a function of different geometrical ratios such as R / H 0 , W 0 / H 0 and H F / H 0 and the rheology of the material, specifically the flow index n . Results of the model were validated by measuring the width increase of a calendered polymeric material over a range of feed thickness, widths, gaps, roll speeds, on two sheeters of different radius. Fairly good results were obtained when the model results were compared with experimental data.

An integral model of microbial inactivation taking into account memory effects: power-law memory kernel.

In this article, we propose an alternative framework for the description of non-log-linear thermal inactivation of microorganisms. The proposed framework generalizes classical views by explicitly taking into account memory effects, such as those often associated with cumulative cell damage or progressive cell adaptation. Within this general framework, specialized memory models can be easily accommodated to describe different modes of microbial response to previous thermal stresses. In this introductory study, the advantages and limitations of the simplest nontrivial memory model, the power-law memory model, were explored. Our results indicate that for isothermal treatments the assumption of power-law memory leads to a simple solution that is known to describe a large number of non-log-linear survival curves. For nonisothermal treatments, the power-law memory model leads to predictions that agree well with experimental data. This research may lead to new insights into predictive microbiology with a new appreciation for the importance of memory effects.

Universal Scaling Law for the Collapse of Viscous Nanopores

Below a threshold size, a small pore nucleated in a fluid sheet will contract to minimize the surface energy. Such behavior plays a key role in nature and technology, from nanopores in biological membranes to nanopores in sensors for rapid DNA and RNA sequencing. Here we show that nanopores nucleated in viscous fluid sheets collapse following a universal scaling law for the pore radius. High-fidelity numerical simulations reveal that the scaling is largely independent of the initial conditions, including the size, shape, and thickness of the original nanopore. Results further show that the scaling law yields a constant speed of collapse as observed in recent experiments. Nanopores in fluid sheets of moderate viscosity also attain this constant terminal speed provided that they are sufficiently close to the singularity.

Contraction of Surfactant-Laden Pores

The contraction of surfactant-laden pores at the microscale has implications for natural and technological processes ranging from the collapse of channels in lipid membranes to the stability of foams in the food processing industry. Despite their prevalence, our understanding of the mechanisms of pore contraction in the presence of surfactants remains unclear. These mechanisms have been challenging to study experimentally given the small length scale near the singularity and simulations capable of accurately characterizing the pore dynamics may help enhance our understanding of the process. Here, we use high-fidelity numerical simulations to gain insight into the fluid dynamics and interfacial phenomena underlying the contraction of viscous pores in the presence of an insoluble surfactant. Results show that surfactants accumulate on the advancing front of a collapsing pore due to the uneven deformation of the pore interface. Because of this accumulation, even a small amount of surfactant plays a major role in the way in which a collapsing pore approaches the singularity.

Interfacial phenomena in food materials

K also called as metastin, is the cognate ligand GPR-54 (G-coupled receptor), which was previously an orphan receptor. Kisspeptin consists of 54 amino acids and its biological activity can be localized to the C-terminal segment which is cleaved into C-10, C-13, and C-14 segment. Kisspeptin-GPR-54 interaction stimulates GnRH secretion and has been shown to be essential for the initiation of the pubertal LH surge. A 14 amino acid derivative of kisspeptin (Asp-58-Val59-Ser60-Ala61-Tyr62Asn63-Trp64-Asn65-Ser66-Phe67-Gly68-Leu69-Arg70-Tyr71NH2) was synthesized by solid phase peptide synthesis using F-moc (9-fluorenyl methoxy carbonyl) strategy. Kisspeptin-14 was synthesized on Rinkamide resin after swelling it for 2h. Amino acid coupling steps were carried out by the treatment of deprotected resin with a 3 fold molar excess of F-moc protected amino acid, HBTU (O-Benzotriazole-N,N,N’,N’-tetramethyl-uronium-hexafluoro-phosphate) and HOBt (N-Hydroxybenzotriazole) for 2h at room temperature under constant shaking. Deprotection was carried out using 20% piperidine for 20 min under constant shaking. Between coupling and deprotection, the resin was washed twice with di-methyl formamide followed by three washing of di-chloromethane. Peptide was cleaved out of the resin using the cleavage mixture (Trifluoro acetic acid-82.5%, Thioanisole-5%, Ethanedithiol-5%, Water-10%, Phenol-5%). Kisspeptin peptide was purified by RP-HPLC using a gradient of 65-90% using C-18 column in binary gradient module consisting of 5% acetonitrile in water and a limiting organic solvent. The peptide was recovered directly after lyophilization. Peptide was evaluated for its secondary conformation by performing CD spectroscopy which showed primarily a random coil structure in water which can be induced to adopt more ordered conformation using solvent like tri-fluoroethanol.L hydrolysis of castor oil yields a high value product free from odour, colour and undesired side products, associated with conventional hydrolytic methods. However, use of immobilized lipase is limited by diffusional constraints of conventional two phase reaction media. Smart design of reaction media allowing oil homogenization was carried out in this study for hydrolysis of castor oil using indigenously immobilized lipases. Optimization of various parameters towards complete hydrolysis was carried out in batch experiments. Maximum hydrolysis of 85% was obtained for the reusable immobilized lipase preparation under packed bed conditions. The activity of immobilized enzyme for the said reaction under optimised conditions was observed to be >85% with no loss of activity for upto 10 cycles tested. The product so formed can be further converted to sugar alcohols, estolides, conjugated linolenic acids or lactones either by enzymatic/microbial methods. The advantage of biotransformation allows production of clean materials that find wider applicability and also higher commercial value.A are an important class of Pharmacological agents used for treating infections, which are a major cause of human morbidity and mortality. Although antibiotics were first isolated from fungi and bacteria (natural Source), but over the years more and more synthetic antibiotics are flowing in market. During the last two decades, the development of drug resistance as well as the appearance of undesirable side effects of certain antibiotics has lead to the search of new antimicrobial agent. There is ample of documented evidence which show antibiotic properties in plant extracts. The present study is based on antibacterial and antifungal activity of wildly growing indigenous plants. Aqueous and ethanol extract of different part ( leaves, flower, fruit, root) of Oxalis amara, Argemone maxicana, Datura inoxia, Calatropis procera , Amranthus, Pithecellobium dulce, Ziziphus mauritiana, Croton bonplandianum, Cannibus sativa, Leucaena leucophela, Andographis Peniculata were taken for study, against pathogenic bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and fungus Candida albicans. Results were observed/ calculated by their zone of inhibition after 24 hours by agar plate gel diffusion method. These plants are showing their antibacterial and antifungal activities, differently for different microorganism. This laboratory experiments has shown that plant extracts are effective against a broad spectrum of microbes (Both Gram positive and Gram negative bacteria and fungus) & antibiotics from Plant extracts (Herbal antibiotics) are promising agents for developing newer antibioticsT effect of increased industrialization has adverse impact on the environment thus leading to air pollution and water pollution. The major impact of industrial systems on the environment is the emissions of gaseous, liquid and particulate materials in the atmosphere which leads to air pollution. Air pollution is aggravated now-a-days because of economic development of societies across the world. The category of air emissions include the criteria pollutants given by the Environmental Protection Agency (EPA), USA which include sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), suspended particulate matter (SPM) and lead (Pb) which are significant contributors in the deterioration of public health (USEPA, 1993). Another important category of pollutants is hazardous pollutants such as Volatile Organic Compounds (VOCs), ammonia (NH3), hydrogen sulfide (H2S), etc. which are responsible for major air and water pollution. Out of all listed hazardous pollutants, VOCs are the large group of organic compounds emitted into the atmosphere by a wide range of industries. In fact, VOCs are one of the major pollutants released by the industries which contaminate the atmospheric air and the fresh water resources. This technique is widely used for the removal of VOCs from and air and metal ions from water. The potential of microorganisms in consuming the VOCs as carbon source makes biodegradation and biofiltration an attractive option for the removal of pollutants from the waste air and waste water streams. The work essentially discusses the biodegradation and biofiltration studies using the mixed culture. The work also discusses the essential factors for the development of the laboratory scale biofilter column and the packing material used in the biofiltration studies. The work also details in the various parameters such as effect of time, effect of flow rate, effect of shock loads and effect of bed height to check the performance of biofiltration. The work also incorporates the various applications of biofilters.F enzyme like Superoxide Dismutase (SOD: 1.15.1.1), has wide applications in the industry of pharmaceuticals, cosmetics, food and/or biotechnology. SOD is a primary antioxidant enzyme catalyzing the dismutation of superoxide free radical (O2-) (a disease causing agent). An important requirement for SODs intended for industrial applications is their thermal stability as thermal denaturation is a common cause of enzyme inactivation. In the present study, SOD has been isolated and characterized from Juglans regia (Walnut) kernels. The SOD enzyme obtained has been partially purified into two fractions based on 0-40% and 40-80% saturation level of ammonium sulphate; 0-40% fraction (72.46 Units/mg) having higher specific activity. The temperature optima of the partially purified SOD lied between 35oC to 40oC with thermo stability up to 70oC whereas the optimum value for pH being 5.0 with stability range of 4.0-7.0. All the tested detergents viz; Sodium Lauryl Sulphate (SLS), Cween-20 and Tween-80 and Tween-20 were found to inhibit the activity of enzyme, Cween-20 being most effective. Mg2+ and Ba2+ ions in the form of their respective salts, acted as potential inhibitors with about 50% reduction in enzyme activity. The results obtained herein indicate that J. regia (Walnut) kernel constitute an excellent source of SOD enzyme, which is an effective natural dietery antioxidant. It can be inferred from the present study that J. regia, a functional food, is a promising source of natural antioxidant (SOD) enzyme with potential application in oxidative stress-related diseases. The thermostability of the enzyme further enhances its importance making it industry friendly with high economical feasibility.H is routinely used in the treatment of pulmonary insufficiency and respiratory distress in preterm and term infants and in adults with acute respiratory disease (ARDS). However, in infants, hyperoxia contributes to the development of chronic lung disease (CLD), which is termed bronchopulmonary dysplasia (BPD). The molecular mechanisms of oxygen-mediated lung injury are not understood, but reactive oxygen species (ROS) are the most likely candidates. ROSare also responsible for many other lung diseases such as acute respiratory distress syndrome (ARDS), asthma, emphysema, chronic obstructive pulmonary disease (COPD), and lung cancer. Results from our laboratory demonstrate a novel role for cytochrome P450 (CYP)1A enzymes in the detoxification of ROS-mediated lipid peroxidation products, e.g., F2-isoprostanes. Our major observations are that mice lacking the genes for CYP1A1 or 1A2 are more susceptible to hyperoxic lung injury than wild type mice, with Cyp1a2-null mice being the most sensitive. On the other hand, mice lacking the gene for CYP1B1, are less susceptible to lung injury, suggesting a pro-oxidant role for CYP1B1. Mice pre-treated with the CYP1A inducer (β-napthoflavone (BNF), followed by exposure to hyperoxia leads to protection against lung injury. We also found formation of bulky oxidative lesions (oxidative DNA adducts) in tracheal aspirates of premature infants and adults who received supplemental oxygen, and this was associated with BPD and ARDS, thereby suggesting that these adducts could serve as novel biomarkers of these diseases. Future studies could lead to the development of rational strategies for the prevention/treatment of lung diseases associated with hyperoxia.S seeds of Sesamum indicum contain abundant oil, in particular, large amounts of unsaturated fatty acid oleic and linoleic acids. These unsaturated fatty acids lower the cholesterol level in the body. Because of their effects and antioxidant substances, attention has been paid to sesame seeds as health food. The regulation of fatty acid synthesis in oilseed crops is quite unknown. It is necessary to clarify these points to breed novel varieties with high contents of unsaturated fatty acids. Full-length cDNA libraries prepared from sesame seed of 1 to 3 weeks DAF, were subtracted with cDNAs from plantlets of 4 weeks after seeding. Each of 1,545 cDNA clones was sequenced. The function of novel genes expressed during the early maturation of sesame seeds was studied by the transformation of Arabidopsis thaliana. Thirteen genes for a transcription factor were identified; four were involved in ethylene signaling. Nine genes including aquaporin-like protein, putative uncharacterized novel protein and ethylene response factor were analyzed by overexpression of A. thaliana. A. thaliana overexpression strain for novel protein and aquaporin-like protein genes, respectively showed the increase of unsaturated fatty acids. The localization of these products was investigated by the induction of the expression vectors for GFP fusion protein into onion cells and sesame seeds with a particle gun.E pollution is considered as a side effect of modern industrial society. The presence of man-made (anthropogenic) organic compounds in the environment is a very serious public health problem. Phenol, an organic compound is toxic even at low concentrations and the toxicity of phenols for microbial cells has been investigated. Owing to the toxic nature and consequent health hazard of phenol, the need to remove it from waste waters. Harnessing the potential of microbes to degrade phenol has been an area of considerable study to develop bioremediation approaches, which is considered as “Green Option” for treatment of environmental contaminants. The optimum conditions for phenol degradation by Pseudomonas putida (NCIM 2102) were at inoculum size (6%v/v), pH (7), temperature (300C), agitation speed (140 rpm), glucose (0.8g/l), ammonium sulphate (1.5g/l), peptone (0.5g/l), and concentration of metal ion Mn2+(0.02 g/l).Central Composite Design (CCD) was employed combining with Response Surface Methodology (RSM) to optimize the physical, chemical parameters for the degradation of phenol by P. putida (NCIM 2102). Response Surface method was using three-levels of physico-chemical parameters like pH, temperature, agitation speed, carbon source (glucose), inorganic nitrogen source (ammonium sulfate) and metal ion (Mn2+) concentration which also enabled the identification of significant effects of interactions for the batch studies. The experimental values are in good agreement with predicted values and the correlation coefficient of physico-chemical parameters was found to be 0.9871, 0.9028 respectively.T Transport Phenomena in Food Materials laboratory at Purdue University seeks to establish the fundamental relationships between the structure of food materials and their mechanical and functional properties as influenced by processing, composition, and environmental conditions. A current research thrust area of this laboratory: Interfacial Phenomena in Foods seeks to establish a detailed understanding of interfacial mechanisms that affect the transport of mass and heat in food matrices, particularly in terms of developing enhanced food materials and processes. Two specific examples of research within this thrust area are: a) precise control of particle size during processing (e.g. emulsification, spray drying, microencapsulation, and nanomaterials) and storage (e.g. microsintering and coalescence) via modulation of dynamic interfacial conditions; and b) identifying novel capillary and interfacial mechanisms for enhancing drying rates in porous food matrices. Advances in this area enabled by insights achieved through combinations of experimental tools (such as high-speed visualization and laser Doppler velocimetry) and recent computational modeling tools (such as first-principles approaches and direct numerical simulations) will be presented.

Drop Formation in Non-Newtonian Jets at Low Reynolds Number

The major objective of this work is to develop accurate computational models to predict evolution of shear thinning liquid jets. A secondary objective is to investigate the formation of satellite drops, and to determine the conditions under which their diameter can be controlled. The theoretical approach of Galerkin-finite element analysis is used solve the complete two-dimensional set of axisymmetric governing equations and the kinematic and dynamic boundary conditions at the free surface. The effect of shear thinning behavior on break-up is studied in detail, in the case of an infinitely long non-Newtonian jet. It is found that the shear thinning behavior may be useful in controlling satellite drop sizes. (We observe that increasing the shear thinning behavior at moderate Reynolds number (Re = 5) leads to an initial increase in the satellite drop size, followed by a subsequent decrease.) Experimental validation for the theory is then presented for the case of a shear thinning non-Newtonian jet. The experimental fluid is pumped through a capillary and drop shapes are obtained using a high speed camera. The experimentally obtained shapes are compared to those predicted by theory with results found to be in good agreement.Copyright