102 research outputs found
Guanidinium containing Poly(methacrylamide)s for non-viral gene delivery
Guanidinium nach der bahnbrechenden Entdeckung seiner Funktion bei der Zellpenetration des Tat-Proteins von HIV-1 zunehmend anerkannt, was einen neuen Weg fĂŒr die Entwicklung von Guanidinium-reichen Transportern eröffnete. Abgesehen von der FĂ€higkeit zur Zellpenetration wurde festgestellt, dass Guanidinium spezielle Wechselwirkungen mit NukleinsĂ€uren hervorrufen kann. Daher wurden Guanidinium-reiche Transporter fĂŒr die nicht-virale GenĂŒbertragung verwendet. Aufgrund der strukturellen und funktionellen Freiheit polymerer Vektoren wurden Guanidiniumgruppen auch in Polymerketten eingebaut und in verschiedenen Studien auf nicht-viralen Gentransport untersucht. Das Potenzial von GCPs fĂŒr die nicht-virale GenĂŒbertragung wurde jedoch noch nicht vollstĂ€ndig aufgeklĂ€rt. Bisher umfassten die meisten EntwĂŒrfe fĂŒr polymere Vektoren primĂ€re, sekundĂ€re und tertiĂ€re Amingruppen als Quelle der kationischen Ladung. Auf der anderen Seite gibt es fĂŒr GCPs noch viel mehr zu entdecken. Daher zeigt die vorgestellte Arbeit prominente Studien zu GCPs fĂŒr den nicht-viralen Gentransfer. Jedes Kapitel illustrierte unterschiedliche Polymerdesigns, indem es die Vielseitigkeit der RAFT-Polymerisation betonte. Die Polymerdesigns wurden unter Verwendung von Methacrylamid-Monomeren mit bioinspirierten Seitengruppen erstellt, um die Polymervektoren mit maximaler Leistung zu erhalten
Incorporation of indole significantly improves the transfection efficiency of guanidiniumâcontaining poly(methacrylamide)s
Abstract A highly efficient transfection agent is reported that is based on terpolymer consisting of N â(2âhydroxypropyl)methacrylamide (HPMA), N â(3âguanidinopropyl) methacrylamide (GPMA), and N â(2âindolethyl)methacrylamide monomers (IEMA) by analogy to the amphipathic cellâpenetrating peptides containing tryptophan and arginine residues. The incorporation of the indoleâbearing monomer leads to successful plasmid DNA condensation even at a nitrogenâtoâphosphate (N/P) ratio of 1. The hydrodynamic diameter of polyplexes is determined to be below 200 nm for all N/P ratios. The transfection studies demonstrate a 200âfold increase of the transgene expression in comparison to P(HPMAâcoâGPMA) with the same guanidinium content. This study reveals the strong potential of the indole group as a sideâchain pendant group that can increase the cellular uptake of polymers and the transfection efficiency of the respective polyplexes
Indole, phenyl, and phenol Groups: The role of the comonomer on gene delivery in guanidinium containing methacrylamide terpolymers
Abstract This report highlights the importance of hydrophobic groups mimicking the side chains of aromatic amino acids, which are tryptophan, phenylalanine, and tyrosine, in guanidinium bearing poly(methacrylamide)s for the design of nonâviral gene delivery agents. Guanidinium containing methacrylamide terpolymers are prepared by aqueous reversible additionâfragmentation chain transfer ( a RAFT) polymerization with different hydrophobic monomers, N â(2âindolethyl)methacrylamide (IEMA), N âphenethylmethacrylamide (PhEMA), or N â(4âhydroxyphenethyl)methacrylamide (PhOHEMA) by aiming similar contents. The wellâdefined polymers are obtained with a molar mass of â15â000 g mol â1 and â1.1 dispersity. All terpolymers demonstrate almost comparable in vitro cell viability and hemocompatibility profiles independent of the type of side chain. Although they all form positively charged, enzymatically stable polyplexes with plasmid DNA smaller than 200 nm, the incorporation of the IEMA monomer improve these parameters by demonstrating a higher DNA binding affinity and forming nanoassemblies of about 100 nm. These physicochemical characteristics are correlated with increased transfection rates in CHOâK1 cells dependent on the type of the monomer and the nitrogen to phosphate (N/P) ratio of the polyplexes, as determined by luciferase reporter gene assays
Comparison of suction and oedometer methods for the measurement of swell pressure
In this paper, a thermocouple psychrometric technique is used to measure soil suction and assess the reliability of a swell pressure prediction method. Kaolinite-bentonite clay mixtures were prepared to obtain expansive soils with a wide range of plasticities. Suction measurements using thermocouple psychrometers and constant volume swell tests in oedometers were made on statically compacted :specimens. Soil suction-water content relationships were evaluated. The results indicate a linear relationship between the logarithm of initial soil suction and swell pressure measured in the oedometer. it has been shown that the method proposed by Johnson & Snethen for the prediction of swell pressure using suction measurements overestimates the ultimate swell pressure
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