Publications by authors named "Michael Neu"

The purpose of this study was to evaluate the number of segments per beam for intensity-modulated radiation therapy (IMRT) treatments and its effects on the plan quality, treatment delivery time, machine quality assurance, and machine maintenance. We have retrospectively analyzed 24 patients treated with IMRT. Five were selected within each of the following regions: head and neck, thoracic, abdomen, and prostate.

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Background: Cell-penetrating peptides (CPPs) could potentially be used as vectors for intracellular delivery of proteins, peptides and nucleic acids. The present study examined different CPPs, such as TAT-derived and arginine rich sequences, as well as model amphiphilic peptide, with respect to transfection efficiency of pegylated polyethylenimine (PEI) in A549, Calu-3 cells and in mice after intra-tracheal administration.

Methods: The conjugates were prepared by the coupling of CPPs to PEI via a heterobifunctional polyethylene glycol (PEG) linker, resulting in the bioconjugates CPP-PEG-PEI.

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Knowledge of the influence of targeting ligands on pharmacokinetics and biodistribution of polymeric nonviral vectors is presently limited. We investigated the properties of three structurally different conjugates of polyethylenglycol-modified polyethylenimine coupled to the HER2 specific antibody Trastuzumab. Unlike polyethylenimine, conjugates formed small (100-230 nm) DNA polyplexes with zeta-potentials of +/- 2 mV at a broad range of N/P ratios.

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Copolymers consisting of branched PEI 25 kDa grafted with high molecular weight PEG at a low degree of substitution were successfully synthesized using a simple two-step procedure. The resulting AB-type and ABA-type copolymers were tested for cytotoxicity and DNA condensation and complexation properties. Their polyplexes with plasmid DNA were characterized in terms of DNA size and surface charge, transfection efficiency and blood compatibility.

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Crosslinked poly(ethylene imine) (PEI) polyplexes for intracellular DNA release were generated using a low molecular weight crosslinking reagent, Dithiobis(succinimidyl propionate) (DSP). Disulfide bonds of the crosslinked polyplexes were susceptible to intracellular redox conditions and DNA release was observed using an ethidium bromide exclusion assay and dynamic light scattering. Transfection experiments were performed to elucidate the effect of extra- and intracellular redox conditions.

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Stabilized PEI/DNA polyplexes were generated by cross-linking PEI with biodegradable disulfide bonds. The reaction conversion of different PEIs with the amine reactive cross-linker dithiobis(succinimidyl propionate) (DSP) was investigated, and the molecular weight of the reaction products was identified. Light scattering and microelectrophoresis were employed to assess size and zeta potential of the resulting polyplexes.

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Polyplexes between siRNA and poly(ethylene imine) (PEI) derivatives are promising nonviral carriers for siRNA. The polyplex stability is of critical importance for efficient siRNA delivery to the cytoplasm. Here, we investigate the effect of PEGylation at a constant ratio ( approximately 50%) on the biophysical properties of the polyplexes.

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The continually increasing wealth of knowledge about the role of genes involved in acquired or hereditary diseases renders the delivery of regulatory genes or nucleic acids into affected cells a potentially promising strategy. Apart from viral vectors, non-viral gene delivery systems have recently received increasing interest, due to safety concerns associated with insertional mutagenesis of retro-viral vectors. Especially cationic polymers may be particularly attractive for the delivery of nucleic acids, since they allow a vast synthetic modification of their structure enabling the investigation of structure-function relationships.

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