Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

Ogris, Manfred; Kotha, Arun K.; Tietze, Nicole; Wagner, Ernst; Palumbo, Fabio Salvatore; Giammona, Gaetano; Cavallaro, Gennara

doi:10.1007/s11095-007-9403-4

Cited by 10 publications

(4 citation statements)

References 18 publications

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“…In contrast, LPEI and BPEI complexes resulted in an increase in liver enzyme levels, indicating beginning necrotic changes in liver tissue already after 24 h consistent with previous literature. 27,37 The…”

Section: Discussionmentioning

confidence: 99%

Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer

et al. 2007

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“…Low molecular weight linear PEI-grafted cyclodextrin, polyaspartamide, chitosan, and dextrane have also been used as highly efficient and less toxic gene carriers − . However, although many polyaspartamide-derived polycations have been applied to in vitro gene delivery, the transfection efficiencies are often relatively low − . We here report oligo-ethylenimine brushes, a new kind of polycation, as polymer gene delivery vectors.…”

Section: Introductionmentioning

confidence: 97%

Polyaspartamide-Based Oligo-ethylenimine Brushes with High Buffer Capacity and Low Cytotoxicity for Highly Efficient Gene Delivery

et al. 2009

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Polyaspartamide-based oligo-ethylenimine brushes (PASP-EDA, PASP-TEPA, PASP-PEHA, and PASP-PEI 423) were synthesized from polysuccinimide (PSI) via a ring-opening reaction with N-Boc protected ethylenediamine, tetraethylenepentamine, pentaethylenehexamine, and linear polyethylenimine (Mn 423), respectively. PASP-TEPA, PASP-PEHA, and PASP-PEI 423 possess high buffer capacity between pH 5 and pH 7, which is comparable to that of branched PEI 25000. The cytotoxicity assay indicated that they all are less toxic than PEI 25000. At an N/P ratio of above 2, all of the four synthetic polycation brushes can condense plasmid DNA to form small sized (160-400 nm) polyelectrolyte complexes with positive surface charge. The transfection of HEK 293 cells with oligo-ethylenimine brush/pRE Luc polyplexes indicated that the transfection efficiencies increased with increasing the length of oligo-ethylenimine side chains. The luciferase expression with PASP-PEHA and PASP-PEI 423 were as high as or even a little higher than that of PEI 25000. The results demonstrate that polyaspartamide-based oligo-ethylenimine brushes are a very promising class of novel polycations for highly efficient and less toxic gene delivery.

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“…Both, cationic lipids and polycations can induce mild to severe liver damage, mainly microvesicular fatty liver. [ 43 ] The histopathological analysis of examined organs from OH4:DOPE NP4 pDNA lipoplex treated and control animals demonstrated healthy and physiological cell and tissue structures (Figure S22, Supporting Information). In the liver there were no obvious alterations, as no fatty liver degeneration or alteration of hepatocytes was visible.…”

Section: Resultsmentioning

confidence: 99%

Investigating 3R In Vivo Approaches for Bio‐Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide‐Mimicking Ionizable Lipid

Giselbrecht

Pinnapireddy

Alioglu

et al. 2022

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Formulations based on ionizable amino‐lipids have been put into focus as nucleic acid delivery systems. Recently, the in vitro efficacy of the lipid formulation OH4:DOPE has been explored. However, in vitro performance of nanomedicines cannot correctly predict in vivo efficacy, thereby considerably limiting pre‐clinical translation. This is further exacerbated by limited access to mammalian models. The present work proposes to close this gap by investigating in vivo nucleic acid delivery within simpler models, but which still offers physiologically complex environments and also adheres to the 3R guidelines (replace/reduce/refine) to improve animal experiments. The efficacy of OH4:DOPE as a delivery system for nucleic acids is demonstrated using in vivo approaches. It is shown that the formulation is able to transfect complex tissues using the chicken chorioallantoic membrane model. The efficacy of DNA and mRNA lipoplexes is tested extensively in the zebra fish (Danio rerio) embryo which allows the screening of biodistribution and transfection efficiency. Effective transfection of blood vessel endothelial cells is seen, especially in the endocardium. Both model systems allow an efficacy screening according to the 3R guidelines bypassing the in vitro–in vivo gap. Pilot studies in mice are performed to correlate the efficacy of in vivo transfection.

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Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

Cited by 10 publications

References 18 publications

Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer

Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer

Polyaspartamide-Based Oligo-ethylenimine Brushes with High Buffer Capacity and Low Cytotoxicity for Highly Efficient Gene Delivery

Investigating 3R In Vivo Approaches for Bio‐Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide‐Mimicking Ionizable Lipid

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