In vitro and biodistribution examinations of Tc-99m-labelled doxorubicin-loaded nanoparticles

BACKGROUND: Nanoparticles represent promising drug carrier systems. In the case of cytostatics such as doxorubicin, carrier colloid systems as human serum albumin (HSA) nanoparticles, may increase their therapeutic efficiency and decrease their side-effects (toxicity) and any potential multidrug resistance. In the present study, doxorubicin, as a widely used antineoplastic agent, was incorporated into the matrix of human serum albumin and three different particle-sized doxorubicin-loaded HSA nanoparticles were prepared, using a previously described desolvation method. Our objective was to find out if different particle sizes of colloid carriers can allow regarding the given cytostatic agent. MATERIAL AND METHODS: The three prepared nanoparticles were labelled using technetium (Tc-99m) and were tested for their physicochemical colloidal quality, fluctuations, and radiochemical stability. Biodistribution of different-sized radiolabelled colloids were determined by means of scintigraphic imaging studies in healthy male Wistar rats. Images were taken by gamma camera at several times and organ uptakes were estimated by quantitative ROI analysis. RESULTS: In vitro measurements showed that more than 95% of doxorubicin proportion was permanently adsorbed to human serum albumin. Radiolabelled doxorubicin-loaded particles had high-degree and durable labelling efficiency and particle size stability. Biodistribution results had a close correlation to earlier described results of radiocolloids in similar particle size ranges. In vivo examinations verified that colloid carriers have insignificant size fluctuations after an intravenous application and they show the proper distribution according to their particle size. CONCLUSIONS: Our investigations verified that different and stable particle sizes make drug carrier HSA nanoparticles possible to apply different drug targeting in a potential clinical use. Nuclear Med Rev 2011; 14, 2: 55–6

Soil and Slope Stability Study of Geomorphic Landform Profiles versus Approximate Original Contour for Valley Fill Designs

This report presents the findings of geotechnical testing on two material types retrieved from a surface mine site in Logan County, West Virginia, and investigates geomorphic landform design as an alternative in lieu of typical valley fill design and approximate original contour (AOC) surface mine reclamation design. Laboratory testing was carried out according to ASTM standard test methods. The scope of the testing performed involved grain size distribution analysis, hydrometer analysis, saturated shear strength testing under an insitu consolidation load, Atterberg limits including plastic and liquid limits, compaction at three predetermined compaction energies, and rigid wall permeameter hydraulic conductivity testing. Data was evaluated and analyzed to find to what degree the material particles moved under certain hydraulic gradients and if the particle movement affected the shear strength of the samples. The objectives of the testing were to understand the movement and behavior of small diameter soil particles at a valley fill and use the strength values as input parameters into several modules of GeoStudio(TM) for numerical slope stability modeling.;The numerical modeling involved geomorphic design for a proposed valley fill in southern West Virginia using commercial software following the Geofluv RTM method. A comprehensive seepage and slope stability analysis was then developed using the SEEP/W, SIGMA/W, and SLOPE/W modules of GeoStudio2007(TM) for assessing the groundwater flow characteristics of the blasted, unweathered sandstone fill, an insitu load calculation, and the resultant limit equilibrium analysis of slope stability (static factor of safety). These analyses were performed for both the AOC and geomorphic fill designs.;The cumulative analysis for the geomorphic valley fill alternative design yielded the highest factors of safety. Most cases produced factors of safety over 2.0. The failure locations were sought out to produce the lowest factors of safety for the structure. None of the factors of safety modeled yielded factors of safety under 1.0 for the geomorphic design. The results imply that the geomorphic design can remain very stable when a range of hydrologic conditions and geometries are applied.;Regulations require that reclaimed slope factors of safety must remain above 1.5. The analyses performed showed that the AOC valley fill design could withstand insitu loads and produced slope angles under most hydrologic conditions analyzed. Elevated pore pressures tended to result at the toe of the slope, and decreased the factor of safety. The most critical scenario was a fully saturated toe which yielded a factor of safety of 0.50.;If particle transport can occur and alter toe pore pressures, it is possible that some small slope failure may occur. The gradations that were found for the unweathered well graded sand with silt fill material showed that particle transport would not be a significant concern. The gradations that were found for the range of cases analyzed for the unweathered well graded sand with silt showed aggregation phenomena which could have implications on the long term stability of the earthen structures

Use of instrumental methods in experimental pharmaceutical research

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Cercetarea farmaceutică experimentală (CFE) implică dezvoltarea, testarea și evaluarea produse farmaceutice. Metodele instrumentale sunt tehnici analitice avansate folosite în acest domeniu pentru a investiga toate caracteristicile și parametrii de calitate ale substanțelor și formelor farmaceutice (SF și FF). Scopul lucrării. Evaluarea aplicării metodelor fizico-chimice de analiză în cercetarea și elaborarea medicamentelor. Material și metode. Studiu bibliografic avansat cu utilizarea bazelor de date Medline, Environmental Issues & Policy Index, Environmental Sci & Pollution Mgmt, Scopus (Elsevier), Current Contents, Scirus. Au fost evaluate 114 de surse bibliografice și 34 metode instrumentale de analiză, aplicate la diverse etape de cercetare a medicamentelor, inclusiv a produselor farmaceutice combinate. Rezultate. Majoritatea cercetărilor evaluate descriu mai multe tehnici analitice experimentale. Cele mai frecvent utilizate sunt: cromatografia (HPLC, GC, CSS: descrise în 87% din sursele evaluate) și metodele spectrale (FTIR, UVVIS, RMN, MS: 59% surse), esențiale pentru determinarea concentrațiilor, impurităților, stabilității, separarea și analiza compușilor dintr-o FF; analiza termică (DSC, TGA: 45% surse), care permite evaluarea comportamentului termic, identificarea tranzițiilor și stabilității termice a FF; dispersia dinamică a luminii și analiza laser a particulelor (12% surse) sunt utilizate pentru măsurarea dimensiunii particulelor din suspensii și emulsii, ceea ce este crucial pentru evaluarea stabilității fizice a FF. Concluzii. Au fost evaluate cele mai esențiale metode instrumentale aplicate în CFE, care oferă informații detaliate despre compoziție, structură și proprietăți fizico-chimice ale substanțelor și produselor farmaceutice, indispensabile la dezvoltarea, caracterizarea și optimizarea acestora.Background. Experimental pharmaceutical research (EPR) involves the development, testing and evaluation of pharmaceutical products. Instrumental methods are advanced analytical techniques used in this field to investigate all the characteristics and quality parameters of pharmaceutical substances (PS) and forms (PF). Objective of the study. Evaluation of the application of physico-chemical methods of analysis in the research and development of medicines. Material and methods. Advanced bibliographic study using databases Medline, Environmental Issues & Policy Index, Environmental Sci & Pollution Mgmt, Scopus (Elsevier), Current Contents, Scirus. 114 bibliographic sources and 34 instrumental methods of analysis, applied to various stages of drug research, including combined pharmaceutical products, were evaluated. Results. Most of the reviewed research describes several experimental analytical techniques. The most frequently used are: chromatography (HPLC, GC, CSS: described in 87% of evaluated sources) and spectral methods (FTIR, UV-VIS, NMR, MS: 59% of sources), essential for determining concentrations, impurities, stability, separation and analysis of compounds from a PhF; thermal analysis (DSC, TGA: 45% sources), which allows the evaluation of thermal behavior, identification of transitions and thermal stability of PhF; dynamic light scattering and laser particle analysis (12% sources) are used to measure particle size in suspensions and emulsions, which is crucial for evaluating the physical stability of PhF. Conclusions. The most essential instrumental methods applied in EPR have been evaluated, which provide detailed information on the composition, structure and physicochemical properties of pharmaceutical substances and products, indispensable for their development, characterization and optimization

Packaging biological cargoes in mesoporous materials: Opportunities for drug delivery

Introduction: Confinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants.Areas covered: Mesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments.Expert opinion: The SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed

Thermooxidative stability of PMMA composites

Tato práce se zabývá studiem termooxidační stability kompozitů polymethylmethakrylátu (PMMA) plněného mikro a nanočásticemi siliky. V připravených vzorcích byly použity různé objemové zlomky a různé velikosti částic siliky. Studium stability bylo prováděno pomocí termogravimetrie, která umožňuje simulovat podmínky termooxidační degradace. Indukční perioda byla stanovena za použití různých rychlostí ohřevu a aplikací izokonverzních metod. Závislosti teplot degradací na rychlostech ohřevu sloužily pro určení parametrů odvozených ze čtyř různých teplotních funkcí, které dovolují předpověď stability materiálu (indukční periody) při zvoleném rozsahu teplot. Zjištěné výsledky ukazují, že větší částice siliky snižuji stabilitu PMMA, zatímco nanočástice v nízkých koncentracích ji nijak neovlivňují.In this work the thermooxidative stability of poly(methyl metacrylate) (PMMA) composites reinforced with silica micro and nanoparticles was studied. Different volume fractions and particles sizes of silica particles were used. PMMA/silica composites were analysed by thermogravimetry which simulated the conditions of thermooxidative degradation. The induction periods were determined using different heating rates and applying the isoconversional methods. The dependence of degradation temperatures on heating rates were used for the determination of adjustable parameters derived for four different temperature functions allowing the prediction of material stability (induction periods) at chosen temperatures. Results showed that the larger silica particles destabilized the PMMA structure while smallest nanoparticles at low concentration had no effect on the stability.

On the stability of the generalized, finite deformation correspondence model of peridynamics

A class of peridynamic material models known as constitutive correspondence models provide a bridge between classical continuum mechanics and peridynamics. These models are useful because they allow well-established local constitutive theories to be used within the nonlocal framework of peridynamics. A recent finite deformation correspondence theory (Foster and Xu, 2018) was developed and reported to improve stability properties of the original correspondence model (Silling et al., 2007). This paper presents a stability analysis that indicates the reported advantages of the new theory were overestimated. Homogeneous deformations are analyzed and shown to exibit unstable material behavior at the continuum level. Additionally, the effects of a particle discretization on the stability of the model are reported. Numerical examples demonstrate the large errors induced by the unstable behavior. Stabilization strategies and practical applications of the new finite deformation model are discussed