Sterically stabilized polyionic complex nanogels of chitosan lysate and PEG-b-polyglutamic acid copolymer for delivery of irinotecan active metabolite (SN-38)

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohsen Salmanpour ◽  
Mahvand Saeed-Vaghefi ◽  
Samira Sadat Abolmaali ◽  
Alimohamad Tamaddon
Keyword(s):  
Glutamic Acid ◽  
Active Metabolite ◽  
Drug Loading ◽  
Free Particle ◽  
Hydrolytic Degradation ◽  
Weight Ratio ◽  
Size Exclusion ◽  
Spherical Particles ◽  
Wide Range ◽  
Polyionic Complex

Background:: Polyionic Complex (PIC) nanogels are promising delivery systems with numerous attractions such as simple, fast, and organic solvent-free particle formation and mild drug loading conditions. Among polyelectrolytes, poly (L-amino acid) copolymers such as poly (ethylene glycol)-block-poly (L-glutamic acid) copolymers (PEG-b-PGlu) are interesting biocompatible and biodegradable candidates bearing carboxylic acid functional groups. Objectives:: Aiming to solubilize and to preserve short-acting irinotecan active metabolite (SN38), sterically stabilized PIC nanogels were prepared through electrostatic charge neutralization between PEG-b-PGlu and chitosan lysate, a polycationic natural polymer obtained through digestion of chitosan by hydrogen peroxide oxidation and is soluble in a wide range of pH. Methods:: Synthesis of PEG-b-PGlu was accomplished by N-carboxyanhydride polymerization of γ -benzyl L-glutamic acid, which is initiated by methoxy PEG-NH2 and successive debenzylation reaction. Result:: The resulting block copolymer was characterized by FTIR, 1H-NMR, and Size Exclusion Chromatography (SEC). Self-assembling properties of the PIC nanogels were investigated by pyrene assay, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM), indicating formation of homogeneous spherical particles with a mean size of 28 nm at the PEG-b-PGlu concentrations/LMWC weight ratio of 5:1. Upon direct loading of SN38, the drug solubility enhanced more than 4×103 folds with a mean loading efficiency of 89% and the drug loading of 30%. PIC nanogels exhibited zeta potential of +1 mV, acceptable biocompatibility, and superior cytotoxicity in murine colorectal carcinoma (CT26 cell line) compared to free drug. Conclusion:: In addition, the PIC nanogels provided SN38 protection against hydrolytic degradation in physiologic condition. Conclusively, the well-tuned PIC nanogels are suggested as a potential biocompatible nanocarrier for SN38 delivery.

Atomistic-Continuum Modeling of the Mechanical Properties of Silica/Epoxy Nanocomposite

2011 ◽  
Vol 134 (1) ◽  
Author(s):  
Bohayra Mortazavi ◽  
Julien Bardon ◽  
Said Ahzi ◽  
Akbar Ghazavizadeh ◽  
Yves Rémond ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Amorphous Silica ◽  
Weight Ratio ◽  
Volume Ratio ◽  
Md Simulations ◽  
Spherical Particles ◽  
Constant Weight ◽  
Epoxy Nanocomposite ◽  
Axial Tensile ◽  
Wide Range

In this study, a hierarchical multiscale homogenization procedure aimed at predicting the effective mechanical properties of silica/epoxy nanocomposites is presented. First, the mechanical properties of the amorphous silica nanoparticles are investigated by means of molecular dynamics (MD) simulations. At this stage, the MD modeling of three-axial tensile loading of amorphous silica is carried out to estimate the elastic properties. Second, the conventional twp phase homogenization techniques such as finite elements (FE), Mori-Tanaka (M-T), Voigt and Reuss methods are implemented to evaluate the overall mechanical properties of the silica/epoxy nanocomposite at different temperatures and at constant weight ratio of 5%. At this point, the mechanical properties of silica obtained in the first stage are used as the inputs of the reinforcing phase. Comparison of the FE and M-T results with the experimental results in a wide range of temperatures reveals fine agreement; however, the FE results are in better agreement with the experiments than those obtained by M-T approach. Additionally, the results predicted by FE and M-T methods are closer to the lower bound (Reuss), which is due to lowest surface to volume ratio of spherical particles.

scholarly journals XYLOOLIGOSACCHARIDES FROM AGRICULTURAL BY-PRODUCTS: CHARACTERISATION, PRODUCTION AND PHYSIOLOGICAL EFFECTS

2017 ◽  
Vol 11 (3) ◽  
Author(s):  
L. Kaprelyants ◽  
O. Zhurlova ◽  
T. Shpyrko ◽  
L. Pozhitkova
Keyword(s):  
High Performance ◽  
Hydrolytic Degradation ◽  
Pharmaceutical Preparations ◽  
Size Exclusion ◽  
Human Consumption ◽  
Physiological Properties ◽  
High Cholesterol Level ◽  
Wide Range ◽  
The Rich ◽  
By Products

The current study is a review of characteristics, production, physiological properties and application of xylooligosaccharides (XOS). XOS are the carbohydrates, their molecules are built from xylose residues linked mainly by в-(1→4)-glycoside bonds. Xylan is important for plant cell walls and is widely spread component in agricultural by-products. XOS are products of xylan hydrolytic degradation, and exhibiting the high prebiotic potential. The XOS preparation of wheat and rye bran stimulated the cells accumulation ‑ 1,4∙1010 CFU/cm3 of L. аcidophilus and 9,2∙1010 CFU/cm3 of В. bifidum. A difference in XOS molecules branching causes a wide range of their physiological properties: antioxidant, immunomodulation, antimicrobial, anti-inflammatory, anticarcinogenic. XOS can reduce high cholesterol level and triglycerides in blood plasma. XOS application reviewed in this article opens new perspectives on its potential use for human consumption. The rich sources of xylan are wheat, rye and barley bran, rice husk, wheat straw, corncobs, cotton stalk. Industrial way of XOS production includes chemical or enzymatic hydrolysis with following purification. Chemical methods are based on hydrothermal pretreatment and acidic or alkali extraction. Obtained oligosaccharides have a wide range of polymerization degree (DP) from 2 to 20. Enzymatic methods include fermentation with xylanase that allow controlling the XOS accumulation with certain DP. The different chromatographic purification after hydrolysis is used for analytical purposes. There are anion-exchange, size-exclusion, affinity, size-exclusion high-performance liquid chromatography. In addition, biomethods are preferred for XOS used in food, because such preparations do not contain monosaccharides and furfural as contaminants. XOS are stable in a wide range of temperature and pH, justifying the development of new synbiotics generation. Most widely XOS are used in production of functional products and pharmaceutical preparations. But they are also applied in cosmetic, agricultural and mixed feed industries.

scholarly journals Novel Biodegradable Polyanhydrides Based on Betulin Disuccinate and Sebacic Acid for Medical Purpose

Proceedings ◽  
2020 ◽  
Vol 67 (1) ◽  
pp. 17
Author(s):  
Daria Niewolik ◽  
Barbara Bednarczyk-Cwynar ◽  
Piotr Ruszkowski ◽  
Katarzyna Jaszcz
Keyword(s):  
Drug Delivery ◽  
Cell Lines ◽  
Hydrolytic Degradation ◽  
Sebacic Acid ◽  
Size Exclusion ◽  
Scanning Calorimetry ◽  
Melt Polycondensation ◽  
Wide Range ◽  
The Us ◽  
Exclusion Chromatography

The paper describes synthesis and the characterization of novel biodegradable betulin-based polyanhydrides, exhibiting anti-cancer activity. Polyanhydrides were obtained by a melt polycondensation of a disuccinate betulin (3,28-di-O-succinyl betulin) and sebacic acid with the use of acetic anhydride. Mentioned polyanhydrides were then thoroughly characterized by 1H NMR and 13C NMR, size exclusion chromatography, differential scanning calorimetry and FT-IR spectroscopy. The content of sebacic acid in obtained copolymers was from 20 to 80 wt%. The use of sebacic acid as a comonomer increases the crystallinity of polymers. Under physiological conditions copolymers undergo hydrolytic degradation to betulin disuccinate, whose biological activity is known and confirmed and to sebacic acid approved by the US Food and Drug Administration (FDA) for use in drug delivery systems. Polyanhydrides were also tested for cytostatic activity against a wide range of cancer cell lines (HeLa, A-549, U-87MG, KB and HepG2), proving its efficiency in inhibiting the growth of selected cell lines. Obtained polymers can be used as carriers in drug delivery system, in form of microspheres. Microspheres with diameter within the range of Dn = 15–30 µm were prepared by using emulsion (O/W) solvent evaporation method.

Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

2018 ◽  
Vol 18 (2) ◽  
pp. 302-311
Author(s):  
Shulin Dai ◽  
Yucheng Feng ◽  
Shuyi Li ◽  
Yuxiao Chen ◽  
Meiqing Liu ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Drug Carrier ◽  
Drug Loading ◽  
Drug Carriers ◽  
Cancer Drug ◽  
Drug Release Profile ◽  
Sustained Drug Release ◽  
Anti Cancer ◽  
Physical Interactions

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. </P><P> Aims/Methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

scholarly journals Effect of Posttranslational Modifications on the Structure and Activity of FTO Demethylase

2021 ◽  
Vol 22 (9) ◽  
pp. 4512
Author(s):  
Michał Marcinkowski ◽  
Tomaš Pilžys ◽  
Damian Garbicz ◽  
Jan Piwowarski ◽  
Damian Mielecki ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Size Exclusion Chromatography ◽  
Posttranslational Modifications ◽  
Size Exclusion ◽  
Saxs Data ◽  
Wide Range ◽  
Exclusion Chromatography ◽  
Demethylase Activity ◽  
Structure And Activity

The FTO protein is involved in a wide range of physiological processes, including adipogenesis and osteogenesis. This two-domain protein belongs to the AlkB family of 2-oxoglutarate (2-OG)- and Fe(II)-dependent dioxygenases, displaying N6-methyladenosine (N6-meA) demethylase activity. The aim of the study was to characterize the relationships between the structure and activity of FTO. The effect of cofactors (Fe2+/Mn2+ and 2-OG), Ca2+ that do not bind at the catalytic site, and protein concentration on FTO properties expressed in either E. coli (ECFTO) or baculovirus (BESFTO) system were determined using biophysical methods (DSF, MST, SAXS) and biochemical techniques (size-exclusion chromatography, enzymatic assay). We found that BESFTO carries three phosphoserines (S184, S256, S260), while there were no such modifications in ECFTO. The S256D mutation mimicking the S256 phosphorylation moderately decreased FTO catalytic activity. In the presence of Ca2+, a slight stabilization of the FTO structure was observed, accompanied by a decrease in catalytic activity. Size exclusion chromatography and MST data confirmed the ability of FTO from both expression systems to form homodimers. The MST-determined dissociation constant of the FTO homodimer was consistent with their in vivo formation in human cells. Finally, a low-resolution structure of the FTO homodimer was built based on SAXS data.

scholarly journals Human Plasma and Recombinant Hemopexins: Heme Binding Revisited

2021 ◽  
Vol 22 (3) ◽  
pp. 1199
Author(s):  
Elena Karnaukhova ◽  
Catherine Owczarek ◽  
Peter Schmidt ◽  
Dominik J. Schaer ◽  
Paul W. Buehler
Keyword(s):  
Protein S ◽  
Soret Band ◽  
Cell System ◽  
Size Exclusion ◽  
Heme Binding ◽  
Systematic Analysis ◽  
Molar Ratios ◽  
Recombinant Production ◽  
Wide Range ◽  
Exclusion Chromatography

Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin (the term “heme” is used in this article to denote both the ferrous and ferric forms). During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), size-exclusion chromatography (SEC)-HPLC, and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX–heme interactions to approximate physiological conditions (from extremely low to more than two-fold heme molar excess over the protein). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggest more than one binding site in both plasma and rhHPX. Furthermore, our study provides a useful analytical platform for the detailed characterization of HPX–heme interactions and potentially novel HPX fusion constructs.

scholarly journals Anodic Titanium Dioxide Nanotubes for Magnetically Guided Therapeutic Delivery

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Morteza Hasanzadeh Kafshgari ◽  
Delf Kah ◽  
Anca Mazare ◽  
Nhat Truong Nguyen ◽  
Monica Distaso ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Hela Cells ◽  
Release Kinetics ◽  
Drug Loading ◽  
Oxide Nanoparticles ◽  
Site Specific ◽  
Therapeutic Drugs ◽  
Wide Range

Abstract Hollow titanium dioxide (TiO2) nanotubes offer substantially higher drug loading capacity and slower drug release kinetics compared to solid drug nanocarriers of comparable size. In this report, we load TiO2 nanotubes with iron oxide nanoparticles to facilitate site-specific magnetic guidance and drug delivery. We generate magnetic TiO2 nanotubes (TiO2NTs) by incorporating a ferrofluid containing Ø ≈ 10 nm iron oxide nanoparticles in planar sheets of weakly connected TiO2 nanotubes. After thermal annealing, the magnetic tubular arrays are loaded with therapeutic drugs and then sonicated to separate the nanotubes. We demonstrate that magnetic TiO2NTs are non-toxic for HeLa cells at therapeutic concentrations (≤200 µg/mL). Adhesion and endocytosis of magnetic nanotubes to a layer of HeLa cells are increased in the presence of a magnetic gradient field. As a proof-of-concept, we load the nanotubes with the topoisomerase inhibitor camptothecin and achieve a 90% killing efficiency. We also load the nanotubes with oligonucleotides for cell transfection and achieve 100% cellular uptake efficiency. Our results demonstrate the potential of magnetic TiO2NTs for a wide range of biomedical applications, including site-specific delivery of therapeutic drugs.

scholarly journals Validation of an HPLC–MS/MS Method for the Determination of Plasma Ticagrelor and Its Active Metabolite Useful for Research and Clinical Practice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 278
Author(s):  
Jennifer Lagoutte-Renosi ◽  
Bernard Royer ◽  
Vahideh Rabani ◽  
Siamak Davani
Keyword(s):  
Active Metabolite ◽  
Plasma Concentrations ◽  
Antiplatelet Agent ◽  
High Plasma ◽  
Therapeutic Drug ◽  
Routine Practice ◽  
Daily Routine ◽  
Limit Of Quantification ◽  
Wide Range

Ticagrelor is an antiplatelet agent which is extensively metabolized in an active metabolite: AR-C124910XX. Ticagrelor antagonizes P2Y12 receptors, but recently, this effect on the central nervous system has been linked to the development of dyspnea. Ticagrelor-related dyspnea has been linked to persistently high plasma concentrations of ticagrelor. Therefore, there is a need to develop a simple, rapid, and sensitive method for simultaneous determination of ticagrelor and its active metabolite in human plasma to further investigate the link between concentrations of ticagrelor, its active metabolite, and side effects in routine practice. We present here a new method of quantifying both molecules, suitable for routine practice, validated according to the latest Food and Drug Administration (FDA) guidelines, with a good accuracy and precision (<15% respectively), except for the lower limit of quantification (<20%). We further describe its successful application to plasma samples for a population pharmacokinetics study. The simplicity and rapidity, the wide range of the calibration curve (2–5000 µg/L for ticagrelor and its metabolite), and high throughput make a broad spectrum of applications possible for our method, which can easily be implemented for research, or in daily routine practice such as therapeutic drug monitoring to prevent overdosage and occurrence of adverse events in patients.

scholarly journals Tunable Crystalline Phases in UV-Curable PEG-Grafted Ladder-Structured Silsesquioxane/Polyimide Composites

Materials ◽  
2020 ◽  
Vol 13 (10) ◽  
pp. 2295 ◽  
Author(s):  
Ryung Il Kim ◽  
Ju Ho Shin ◽  
Jong Suk Lee ◽  
Jung-Hyun Lee ◽  
Albert S. Lee ◽  
...  
Keyword(s):  
Polymer Composites ◽  
Surface Properties ◽  
Weight Ratio ◽  
Hybrid Polymer ◽  
Water Contact ◽  
Uv Curable ◽  
Wide Range ◽  
Drastic Increase ◽  
Polyimide Composites ◽  
Crystalline Polyethylene

A series of UV-curable hybrid composite blends containing a carboxylic acid functionalized polyimidewith varying amounts of high molecular weight (~1 K) PEG-grafted ladder-structured polysilsesquioxanes copolymerized with methacryl groups were fabricated and their structural, thermal, mechanical, and surface properties characterized. At a composite weight ratio of polyimide above 50 wt.%, a stark shift from amorphous to crystalline polyethylene glycol (PEG) phases were observed, accompanied by a drastic increase in both surface moduli and brittleness index. Moreover, fabricated composites were shown to have a wide range water contact angle, 9.8°–73.8°, attesting to the tunable surface properties of these amphiphilic hybrid polymer composites. The enhanced mechanical properties, combined with the utility of tunable surface hydrophilicity allows for the possible use of these hybrid polymer composites to be utilized as photosensitive polyimide negative photoresists for a myriad of semiconductor patterning processes.

Calculation of the primary trajectories of seeds and other particles in strong winds

1983 ◽  
Vol 219 (1215) ◽  
pp. 217-217
Keyword(s):  
Equations Of Motion ◽  
Aerodynamic Resistance ◽  
Reynolds Numbers ◽  
Spherical Particles ◽  
Spores And Pollen ◽  
General Terms ◽  
Wide Range ◽  
Strong Winds ◽  
Dispersal Distances ◽  
Enormous Number

The movement of variously dense spherical particles representing a variety of seeds, fruits, spores and pollen, and released from rest into arbitrary winds and a gravitational field is discussed in general terms that account in detail for changes in the quasi-static aerodynamic resistance to motion experienced by such particles during aerial flight. A hybrid analytical-empirical law is established which describes this resistance fairly accurately for particle Reynolds numbers in the range 0—60 000 and that allows for the numerical integration of the equations of motion so as to cover a very wide range of flight conditions. This makes possible the provision of a set of four-parameter universal range tables from which the dispersal distances for an enormous number of practical cases may be estimated. One particular case of particle movement in a region of pseudo-thermal convection is also discussed and this shows how a marked degree of deposition concentration may be induced in some circumstances by such a flow. Botanists and ecologists concerned with seed and particle dispersal in the environment may find the universal range tables of particular interest and use. This is because the tables obviate the need for the integration of the equations of motion when dealing with individual cases and permit an estimation of range purely on the basis of the specified quantities of particle size, density and altitude of release, atmospheric wind speed, density and viscosity, and the acceleration due to gravity.

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