scholarly journals Comparative Investigation of Cellular Effects of Polyethylene Glycol (PEG) Derivatives

Polymers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 279
Author(s):  
Ha Pham Le Khanh ◽  
Dániel Nemes ◽  
Ágnes Rusznyák ◽  
Zoltán Ujhelyi ◽  
Pálma Fehér ◽  
...  

Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care products, and the pharmaceutical industry. Their advantageous properties such as chemical stability, low immunogenicity, and high tolerability explain why PEGs are applied in many fields of pharmaceutical formulations including parenteral, topical, ophthalmic, oral, and rectal preparations and also in modern drug delivery systems. Given their extensive use, they are considered a well-known group of chemicals. However, the number of large-scale comparative studies involving multiple PEGs of wide molecular weight range is low, as in most cases biological effects are estimated upon molecular weight. The aim of this publication was to study the action of PEGs on Caco-2 cells and G. mellonella larvae and to calculate the correlation of these effects with molecular weight and osmolality. Eleven PEGs of different molecular weight were used in our experiments: PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 4000, PEG 8000, PEG 10,000, 12,000, and PEG 20,000. The investigated cellular effects included cytotoxicity (MTT and Neutral Red assays, flow cytometry with propidium iodide and annexin V) and autophagy. The osmolality of different molecular weight PEGs with various concentrations was measured by a vapor pressure osmometer OSMOMAT 070 and G. mellonella larvae were injected with the solutions of PEGs. Sorbitol was used as controls of the same osmolality. Statistical correlation was calculated to describe the average molecular weight dependence of the different measured effects. Osmolality, the cytotoxicity assays, flow cytometry data, and larvae mortality had significant correlation with the structure of the PEGs, while autophagosome formation and the proportion of early apoptotic cells showed no statistical correlation. Overall, it must be noted that PEGs must be tested individually for biological effects as not all effects can be estimated by the average molecular weight.

1981 ◽  
Vol 64 (4) ◽  
pp. 999-1007
Author(s):  
Roger C Snyder ◽  
Charles V Breder

Abstract A liquid chromatograph is described for the size exclusion chromatography (SEC) of polyethylene and oligomers. The rigid column packing material was 10 µm diameter porous silica. An infrared spectrophotometer was used as the detector. The chromatograph was designed and operated to minimize the degree of chromatographic peak shape distortion resulting from factors such as system dead volume, detector cell design, sample injection volume, and sample concentration. To compensate for peak spreading and skewing, the chromatographic data were analyzed with an IBM 370/168 computer using an APL program. The molecular weight range covered by this SEC system was 100-500 000. Precision and accuracy of Jhe calculated weight average molecular weight (Mw) values for polyethylene standards over this range were ±3 and s±4%, respectively.


1943 ◽  
Vol 16 (3) ◽  
pp. 493-508
Author(s):  
Paul J. Flory

Abstract Experimental methods for fractionating polyisobutylene and for determining osmotic pressures have been described. The ratio π/c of osmotic pressure to concentration has been found in the case of cyclohexane solutions of polyisobutylene to vary nonlinearly with concentration, contrary to recent theories advanced by Huggins and the writer. The slope of this relationship appears to be independent of molecular weight. Reliable methods for extrapolating π/c to c=0 have been established, enabling the determination of absolute molecular weights with satisfactory precision up to values of about 1,000,000. Molecular weights of polyisobutylenes calculated from Staudinger's equation are too low; the discrepancy is more than ten-fold at high molecular weights. On the basis of data for carefully fractionated samples covering a two-hundred-fold molecular weight range, the intrinsic viscosity is found to be proportional to the 0.64 power of the molecular weight. This decided deviation from Staudinger's “law”cannot in this instance be attributed to nonlinear chain structure, as Staudinger has sought to do in other cases. This dependence of molecular weight on intrinsic viscosity leads to the definition of a “viscosity average”molecular weight which is obtained when the relationship is applied to heterogeneous polymers. The viscosity average is less than the weight average molecular weight, which would be obtained if Staudinger's equation were applicable, and greater than the number average obtained by osmotic or cryoscopic methods.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 929-929 ◽  
Author(s):  
Aizhen Yang ◽  
Jihong Dai ◽  
Raymond B. Birge ◽  
Yi Wu

Abstract Abstract 929 Phagocytosis of apoptotic cells by phagocytes, also known as efferocytosis, is essential for maintaining normal tissue homeostasis and regulating immune responses. Defects in rapid clearance of apoptotic cells lead to the release of immunogenic cellular contents, which may cause tissue damage and autoimmune disease. Phagocytic receptors differentiate apoptotic cells from viable cells by recognizing ‘don't eat- or eat-me’ signals on the cell surface. Recently, we and others have reported the role of uPAR in mediating efferocytosis. In this study, we examined the mechanism by which uPAR recognizes and internalizes apoptotic cells. By flow cytometry-based in vivo and in vitro phagocytosis assay, we found that in knockout mice the lack of uPAR expression on macrophages decreased their apoptotic cell engulfing activity by >35%. Conversely, soluble uPAR and polyclonal anti-uPAR antibodies (Ab) suppressed the internalization of apoptotic cells by macrophages. However, there was no defect in uPAR-/- macrophage uptake of viable cells, suggesting that uPAR plays a specific role in phagocytosis of apoptotic cells. We established a HEK 293 cell line expressing human full-length uPAR (293-uPAR). In these cells, uPAR-mediated phagocytosis of apoptotic cells was completely blocked by annexin V in the presence of calcium. The effect of annexin V was not observed in the absence of calcium, indicating that uPAR internalizes apoptotic cells through a phosphatidylserine pathway. We also found that uPAR-mediated uptake of apoptotic cells was completely prevented under serum-free conditions. To identify plasma proteins that may opsonize the uPAR function, we used immunodepletion method to test three known uPAR-binding proteins, vitronectin, uPA and high molecular weight kininogen (HK). Depletion of HK from serum by a polyclonal anti-HK Ab significantly reduced the engulfment of apoptotic cells by either macrophages or 293-uPAR cells in a co-culture system. In contrast, depletion of vitronectin or uPA from serum had little effect. uPAR is a GPI-anchored protein. Upon sucrose gradient ultracentrifugation, the majority of uPAR molecules were co-localized with membrane-bound HK in lipid rafts. The binding capacity of HK to apoptotic cell surface was further analyzed by flow cytometry. Phycoerythrin-labeled HK bound to apoptotic cells in a concentration-dependent manner, saturating at 300 nM. In contrast, HK did not bind to viable cells at concentrations up to 1200 nM. It is known that HK is a key component of the plasma contact system and that apoptotic cells potentiate factor Xa formation. Our new findings of the uPAR-HK-phosphatidylserine axis in efferocytosis suggest that this pathway may modulate the coagulation cascade on the surface of apoptotic cells. This pathway may also play a role in the pathogenesis of autoimmune and thrombotic disease. Disclosures: No relevant conflicts of interest to declare.


Biologia ◽  
2011 ◽  
Vol 66 (3) ◽  
Author(s):  
Hideki Kajiura ◽  
Hiroki Takata ◽  
Tsunehisa Akiyama ◽  
Ryo Kakutani ◽  
Takashi Furuyashiki ◽  
...  

AbstractThis review describes a new enzymatic method for in vitro glycogen synthesis and its structure and properties. In this method, short-chain amylose is used as the substrate for branching enzymes (BE, EC 2.4.1.18). Although a kidney bean BE and Bacillus cereus BE could not synthesize high-molecular weight glucan, BEs from 6 other bacterial sources produced enzymatically synthesized glycogen (ESG). The BE from Aquifex aeolicus was the most suitable for the production of glycogen with a weight-average molecular weight (M w) of 3,000–30,000 k. The molecular weight of the ESG is controllable by changing the concentration of the substrate amylose. Furthermore, the addition of amylomaltase (AM, EC 2.4.1.25) significantly enhanced the efficiency of this process, and the yield of ESG reached approximately 65%. Typical preparations of ESG obtained by this method were subjected to structural analyses. The average chain length, interior chain length, and exterior chain length of the ESGs were 8.2–11.6, 2.0–3.3, and 4.2–7.6, respectively. Transmission electron microscopy and intrinsic viscosity measurement showed that the ESG molecules formed spherical particles. Unlike starch, the ESGs were barely degraded by pullulanase. Solutions of ESG were opalescent (milky-white and slightly bluish), and gave a reddishbrown color on the addition of iodine. These analyses revealed that ESG shares similar molecular shapes and solution properties with natural-source glycogen. Moreover, ESG had macrophage-stimulating activity and its activity depends on the molecular weight of ESG. We successfully achieved large scale production of ESG. ESG could lead to new industrial applications, such as in the food, chemical, and pharmaceutical fields.


1949 ◽  
Vol 22 (2) ◽  
pp. 494-517 ◽  
Author(s):  
John A. Yanko

Abstract A large-scale precise fractionation of GR-S (X-55) was carried out at 25° C, using a fractional precipitation technique. Nine fractions, each weighing approximately 150 grams and comprising about 11 per cent by weight of the original unfractionated sample, were obtained, with number-average molecular weights varying from 4000 to 1,650,000. High molecular fractions undergo gelation rapidly, even when dried in the absence of light at reduced pressure, and the higher the molecular weight of the fraction, the greater the amount of gel formed. Compared to unfractionated butadiene-styrene copolymers of similar gel contents, the gel portions of the higher molecular fractions had unusually high swelling indices, indicating qualitatively that the average molecular weights between points of effective cross-linking in the three-dimensional gel structure were higher than those found in the past in unfractionated samples of similar gel contents. Through the concentration range studied, the intrinsic viscosity values varied as a straight-line function of the concentration terms for all the fractions. However, the negative slopes of these lines increased as the molecular weight of the fraction increased, demonstrating the greater dependence of the intrinsic viscosity values of the higher molecular fractions on the concentration variable. The relationship between number-average molecular weight, as determined by osmometric measurements, and limiting intrinsic viscosity of the GR-S fractions is given by the equation: [η]0=5.4×10−4 M0.66, which is similar to that obtained by French and Ewart. The μi values calculated from the equation of Huggins were essentially the same (0.35) through the molecular range 12,400 to 723,000.


1975 ◽  
Author(s):  
E. Thaler ◽  
G. Schmer

Five heparin fractions of different molecular weight range were obtained from commercial sodium heparin (Sigma) by gel chromatography on Sephadex G-200. Each fraction was bound separately to Biogel A-15 m by the cyanogen bromide reaction. Microcolumns containing equal amounts of the individual heparin agarose batches were prepared. A protein fraction from human plasma containing antithrombin II/III but no fibrinogen, which was obtained by polyethylene glycol precipitation, was passed through the columns. After extensive washing with 0.15 and 0.3 M buffered sodium chloride antithrombin was eluted with 1.0 M buffered sodium chloride. The uptake of antithrombin did not differ greatly in all five heparin agarose preparations. However, the amount of antithrombin eluted with 1.0 M NaCl varied considerably depending on the insolubilized heparin fraction. Almost no antithrombin activity was eluted from the agarose grafted with the highest molecular weight heparin, while all of the antithrombin was recovered from the agarose with the intermediate molecular weight heparin.Our findings of different affinities of antithrombin to insolubilized heparin in dependance of its molecular weight suggest similar implications for the practical use of heparin in anticoagulant therapy.


1942 ◽  
Vol 15 (1) ◽  
pp. 1-16
Author(s):  
A. R. Kemp ◽  
H. Peters

Abstract 1. Evaporated latex films and Bolivian fine para contain a chloroform-soluble fraction of about 62 per cent, whereas the soluble portion of crepe and smoked sheets is about 86 per cent. The average molecular weight of these sols, which contain the low polymers and “resin”, range from about 130,000 to 180,000, the more soluble type having the lower value. 2. Diffusion and precipitation methods were employed to fractionate R. C. M. A. crepe, and the following data indicate the approximate composition and molecular weight range of the soluble hydrocarbon fractions separated: 3. The chloroform-insoluble portion of crepe contains a nonlinear type of hydrocarbon, judged by x-ray and viscosity studies. These methods show that the chloroform-insoluble portion of ammonia-preserved latex films contain extremely high-molecular rubber hydrocarbon which is easily oriented to give the regular x-ray crystalline pattern for rubber. 4. Freshly tapped latex contains a large proportion of petroleum-ether-soluble fraction, which becomes insoluble in this solvent on standing in the presence of ammonia. Ammonia-preserved latex films are soluble in chloroform or in hexane containing alcohol-acetone or acetic acid; this insolubility is thus an association effect, which is overcome by the addition of a polar solvent. 5. Viscosity studies on fractions of balata and gutta-percha show that their hydrocarbons have an average molecular weight of about 42,000 and cover a narrow polymeric range.


Materials ◽  
2020 ◽  
Vol 13 (5) ◽  
pp. 1068 ◽  
Author(s):  
Rafał Malinowski ◽  
Krzysztof Moraczewski ◽  
Aneta Raszkowska-Kaczor

The results of studies on the uncrosslinked fraction of blends of polylactide and poly(butylene adipate-co-terephthalate) (PLA/PBAT) are presented. The blends were crosslinked by using the electron radiation and triallyl isocyanurate (TAIC) at a concentration of 3 wt %. Two kinds of samples to be investigated were prepared: one contained 80 wt % PLA and the other contained 80 wt % PBAT. Both blends were irradiated with the doses of 10, 40, or 90 kGy. The uncrosslinked fraction was separated from the crosslinked one. When dried, they were subjected to quantitative analysis, Fourier transform infrared spectroscopy (FTIR) measurements, an analysis of variations in the average molecular weight, and the determination of thermal properties. It was found that the electron radiation caused various effects in the studied samples, which depended on the magnitude of the radiation dose and the weight fractions of the components of the particular blends. This was evidenced by the occurrence of the uncrosslinked fractions of different amounts, a different molecular weight distribution, and the different thermal properties of the samples. It was also concluded that the observed effects were caused by the fact that the processes of crosslinking and degradation took place mostly in PLA, while PBAT appeared to be less susceptible to the influence of the electron radiation.


1958 ◽  
Vol 36 (6) ◽  
pp. 952-969 ◽  
Author(s):  
M. M. Huque ◽  
D. A. I. Goring ◽  
S. G. Mason

Viscosity and light-scattering measurements were made on several fractions and two unfractionated samples of cellulose trinitrate. The samples were prepared from bleached ramie, unbleached ramie, and cotton linters. The solvents were acetone and ethyl acetate. Viscosity was measured in a multishear viscometer designed for the purpose. Light-scattering measurements were made in a Brice-Phoenix Light-scattering Photometer modified to accommodate a cell which could be ultracentrifuged.The range of molecular weight investigated was from 6.5 × 105 to 25.0 × 105 The relationship between the z-average mean-square radius of gyration, [Formula: see text] and the z-average molecular weight was approximately linear in both solvents. The ratio of [Formula: see text] (where [Formula: see text] is the value of [Formula: see text] in the unperturbed state) was found constant in acetone but to increase with [Formula: see text] in ethyl acetate. This indicated that, whereas in acetone random coil configuration was attained, a configurational transition occurred in ethyl acetate in the molecular weight range investigated.The value of the exponent a in the relationship between intrinsic viscosity and molecular weight was found to be lower than unity but approximately equal in both solvents.The significance of the experimental data is discussed.


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