scholarly journals The Impact of Polymer Size and Cleavability on the Intravenous Pharmacokinetics of PEG-Based Hyperbranched Polymers in Rats

Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2452
Author(s):  
Nirmal Marasini ◽  
Changkui Fu ◽  
Nicholas L. Fletcher ◽  
Christopher Subasic ◽  
Gerald Er ◽  
...  

A better understanding of the impact of molecular size and linkers is important for PEG-based hyperbranched polymers (HBPs) intended as tailored drug delivery vehicles. This study aimed to evaluate the effects of crosslinker chemistry (cleavable disulphide versus non-cleavable ethylene glycol methacrylate (EGDMA) linkers) and molecular weight within the expected size range for efficient renal elimination (22 vs. 48 kDa) on the intravenous pharmacokinetic and biodistribution properties of 89Zr-labelled HBPs in rats. All HBPs showed similar plasma pharmacokinetics over 72 h, despite differences in linker chemistry and size. A larger proportion of HBP with the cleavable linker was eliminated via the urine and faeces compared to a similar-sized HBP with the non-cleavable linker, while size had no impact on the proportion of the dose excreted. The higher molecular weight HBPs accumulated in organs of the mononuclear phagocyte system (liver and spleen) more avidly than the smaller HBP. These results suggest that HBPs within the 22 to 48 kDa size range show no differences in plasma pharmacokinetics, but distinct patterns of organ biodistribution and elimination are evident.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hangyu Park ◽  
Youngson Choe

Toughened epoxy has been widely used in industrial areas such as automotive and electronics. In this study, nanosized hyperbranched polymers (HBPs) as a flexibilizer are synthesized and embedded into epoxy resin to enhance the toughness and flexibility. Two different HBPs, hyperbranched poly(methylacrylate-diethanolamine) (poly(MA-DEA)) and poly(methylacrylate- ethanolamine) (poly(MA-EA)), were prepared and blended with both epoxy and polyetheramine, a curing agent. The molecular size of HBPs was estimated to be 6 ~ 14 nm in diameter. The molecular weight of HBPs ranges from 1500(1.5 K) to 7000(7.0 K) g/mol. In cured epoxy/HBP blends, no phase separations are occurred, indicating that HBPs possess sufficient miscibility with epoxy. The tensile toughness of the blends increased with changing the molecular weight of HBPs without sacrificing tensile strengths. The impact strength of the blends increases stiffly until the loading % of HBPs in the blends reaches 10 wt%. In addition, the experimental studies showed that impact resistance also increased with an increase in molecular weight of HBPs. The obtained impact resistance of the epoxy/HBP blends with 10 wt% was 270% more effective compared to that of cured neat epoxy.


1975 ◽  
Author(s):  
P. J. Gaffney ◽  
K. Lord ◽  
R. D. Thornes

Brinase (an extract of Aspergillus Oryzae) was shown to rapidly digest human fibrinogen in vitro to aggregable degradation products with a molecular size range of 310,000 to 230,000 the latter fragments being more slowly digested to core fragments, Dbr and Ebr. The fibrinogen polypeptide chain susceptibility to Brinase attack was in the order Aα, γ, Bβ, Lysis of the Bβ chain seems to be the rate limiting step in the conversion of the high molecular weight fragments (MW 310,000–230,000) to the core fragments Dbr and Ebr. The conservation of NH2 terminal Tyrosine during fibrinogen digestion and the very transient existence of D dimer fragments during totally crosslinked fibrin lysis suggest that the carboxy end of the γ chain is prone to Brinase attack. The crosslinked α chains of fibrin, while resistant to plasmin, are vigorously digested by Brinase. The plasma of cancer patients being treated with Brinase contained degraded fibrinogen (lacking intact Aα chains) and their aggregates. These aggregates contained some crosslinked γ chains (γ-γ dimers) suggesting that Brinase in vivo exorcises both a lytic and coagulant effect. Thrombin mediated clots in all the plasmas examined contained no crosslinked α chains. Positive plasma ethanol gelation tests can be explained by the presence of the aggregable high molecular weight fragments observed during the in vitro lysis of fibrinogen by Brinase.


2019 ◽  
Vol 47 (18) ◽  
pp. 9803-9817 ◽  
Author(s):  
Ágnes Dalmadi ◽  
Péter Gyula ◽  
Jeannette Bálint ◽  
György Szittya ◽  
Zoltán Havelda

Abstract RNA interference (RNAi) is mediated by small, 20-24-nt-long, non-coding regulatory (s)RNAs such as micro (mi) and small interfering (si) RNAs via the action of ARGONAUTE (AGO) proteins. High-throughput sequencing of size-separated sRNA pools of plant crude extracts revealed that the majority of the canonical miRNAs were associated with high molecular weight RNA-induced silencing complexes co-migrating with AGO1 (HMW RISC). In contrast, the majority of 24-nt-long siRNAs were found in association with low molecular weight complexes co-migrating with AGO4 (LMW RISC). Intriguingly, we identified a large set of cytoplasmic sRNAs, including mature miRNA sequences, in the low molecular size range corresponding to protein-unbound sRNAs. By comparing the RISC-loaded and protein-unbound pools of miRNAs, we identified miRNAs with highly different loading efficiencies. Expression of selected miRNAs in transient and transgenic systems validated their altered loading abilities implying that this process is controlled by information associated with the diverse miRNA precursors. We also showed that the availability of AGO proteins is a limiting factor determining the loading efficiency of miRNAs. Our data reveal the existence of a regulatory checkpoint determining the RISC-loading efficiencies of various miRNAs by sorting only a subset of the produced miRNAs into the biologically active RISCs.


1966 ◽  
Vol 16 (03/04) ◽  
pp. 384-394 ◽  
Author(s):  
S Cronberg ◽  
B Robertson ◽  
Inga Marie Nilsson ◽  
J.-E Niléhn

Summary43 normal volunteers, 3 patients with thrombophlebitis, and 1 patient with a high platelet adhesiveness and a history of thrombophlebitis have received dextran and its action on the mechanism of haemostasis has been studied. Platelet adhesiveness has been investigated by a slight modification of Hellem’s methods for whole blood and plasma. Dextran with a mean molecular weight of 70,000 produced a markedly lowered platelet adhesiveness together with a moderate prolongation of the Ivy bleeding time. Factor VIII was decreased by about 50% and factor V, factor IX and fibrinogen were decreased slightly more than could be expected from haemodilution alone. No fibrinolysis occurred. Dextran of lower molecular size was less potent. The possible use of dextrans as a thrombosis prophylactic agent is discussed.


Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Hamid Ait Said ◽  
Hassan Noukrati ◽  
Hicham Ben Youcef ◽  
Ayoub Bayoussef ◽  
Hassane Oudadesse ◽  
...  

Three-dimensional hydroxyapatite-chitosan (HA-CS) composites were formulated via solid-liquid technic and freeze-drying. The prepared composites had an apatitic nature, which was demonstrated by X-ray diffraction and Infrared spectroscopy analyses. The impact of the solid/liquid (S/L) ratio and the content and the molecular weight of the polymer on the composite mechanical strength was investigated. An increase in the S/L ratio from 0.5 to 1 resulted in an increase in the compressive strength for HA-CSL (CS low molecular weight: CSL) from 0.08 ± 0.02 to 1.95 ± 0.39 MPa and from 0.3 ± 0.06 to 2.40 ± 0.51 MPa for the HA-CSM (CS medium molecular weight: CSM). Moreover, the increase in the amount (1 to 5 wt%) and the molecular weight of the polymer increased the mechanical strength of the composite. The highest compressive strength value (up to 2.40 ± 0.51 MPa) was obtained for HA-CSM (5 wt% of CS) formulated at an S/L of 1. The dissolution tests of the HA-CS composites confirmed their cohesion and mechanical stability in an aqueous solution. Both polymer and apatite are assumed to work together, giving the synergism needed to make effective cylindrical composites, and could serve as a promising candidate for bone repair in the orthopedic field.


Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1137
Author(s):  
Sascha Stanic ◽  
Thomas Koch ◽  
Klaus Schmid ◽  
Simone Knaus ◽  
Vasiliki-Maria Archodoulaki

Blends of two long-chain branched polypropylenes (LCB-PP) and five linear polypropylenes (L-PP) were prepared in a single screw extruder at 240 °C. The two LCB-PPs were self-created via reactive extrusion at 180 °C by using dimyristyl peroxydicarbonate (PODIC C126) and dilauroyl peroxide (LP) as peroxides. For blending two virgin and three recycled PPs like coffee caps, yoghurt cups and buckets with different melt flow rate (MFR) values were used. The influence of using blends was assessed by investigating the rheological (dynamic and extensional rheology) and mechanical properties (tensile test and impact tensile test). The dynamic rheology indicated that the molecular weight as well as the molecular weight distribution could be increased or broadened. Also the melt strength behavior could be improved by using the two peroxide modified LCB-PP blends on the basis of PODIC C126 or PEROXAN LP (dilauroyl peroxide). In addition, the mechanical properties were consistently enhanced or at least kept constant compared to the original material. In particular, the impact tensile strength but also the elongation at break could be increased considerably. This study showed that the blending of LCB-PP can increase the investigated properties and represents a promising option, especially when using recycled PP, which demonstrates a real “up-cycling” process.


Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 591
Author(s):  
Bożena Grimling ◽  
Bożena Karolewicz ◽  
Urszula Nawrot ◽  
Katarzyna Włodarczyk ◽  
Agata Górniak

Chitosans represent a group of multifunctional drug excipients. Here, we aimed to estimate the impact of high-molecular weight chitosan on the physicochemical properties of clotrimazole–chitosan solid mixtures (CL–CH), prepared by grinding and kneading methods. We characterised these formulas by infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry, and performed in vitro clotrimazole dissolution tests. Additionally, we examined the antifungal activity of clotrimazole–chitosan mixtures against clinical Candida isolates under neutral and acid conditions. The synergistic effect of clotrimazole and chitosan S combinations was observed in tests carried out at pH 4 on Candida glabrata strains. The inhibition of C. glabrata growth reached at least 90%, regardless of the drug/excipient weight ratio, and even at half of the minimal inhibitory concentrations of clotrimazole. Our results demonstrate that clotrimazole and high-molecular weight chitosan could be an effective combination in a topical antifungal formulation, as chitosan acts synergistically with clotrimazole against non-albicans candida strains.


Soil Research ◽  
1969 ◽  
Vol 7 (3) ◽  
pp. 229 ◽  
Author(s):  
JHA Butler ◽  
JN Ladd

Humic acids extracted from soil with sodium pyrophosphate have greater proportions of lower molecular weight material, less acid-hydrolysable amino acid nitrogen contents, but greater carboxyl contents and extinction values (260 and 450 nm) than humic acids extracted subsequently from the same sample with alkali. Humic acids extracted with alkali from fresh soil samples have intermediate values. Extinction values at 260 nm are directly correlated with carboxyl contents for a given soil. Different crop histories have no significant effect on the measured properties of the extracted humic acids. An alkali-extracted humic acid has been fractionated by gel filtration into seven fractions of different nominal molecular weight ranges. As the molecular weights of the fractions increase, both aliphatic C-H (based on infrared absorption at 2900 cm-1) and acid-hydrolysable amino acid contents increase, whereas extinction values at 260 nm and carboxyl contents decrease. The infrared spectra of the high molecular weight fractions have peaks at 1650 and 1510 cm-1 which correlate with acid-hydrolysable amino acid contents and which correspond to amide I and II bands of peptide bonds. Alkaline hydrolysis to split peptide bonds eliminates both these peaks. The spectra also have peaks at 1720 and 1210 cm-1 which correlate with the carboxyl content.


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