Storage stability of optimal liposome–polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery

Ewe, Alexander; Schaper, Andreas; Barnert, Sabine; Schubert, Rolf; Temme, Achim; Bakowsky, Udo; Aigner, Achim

doi:10.1016/j.actbio.2014.02.037

Cited by 67 publications

(59 citation statements)

References 64 publications

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“…The PEI solution was added to the siRNA solution, vortexed, and incubated for 30 min at room temperature. The lipopolyplexes were prepared by incubating equal volumes of PEI/siRNA complexes with liposomes at a PEI/ lipid mass ratio of 5 [25]. To this end, 25 μL polyplex containing 4 μg PEI F25 and 25 μL DPPC liposomes comprising 20 μg lipid were properly mixed by pipetting and vortexing, and incubated for at least 1 h at room temperature prior to use.…”

Section: Liposome Pei Complex and Lipopolyplex Preparationmentioning

confidence: 99%

“…The liposomes DPPC, DPPC/DPPE (85:15 mol/mol), DPPC/DPPG (92:8 mol/mol) were prepared by the hydration/extrusion method as described previously [25]. Five milligram lipid(s) in chloroform/methanol (2:1, v/v) were dried in a round-bottom flask and hydrated with 1 mL sterile dH 2 O.…”

Section: Liposome Pei Complex and Lipopolyplex Preparationmentioning

confidence: 99%

“…Among others, these include the preparation of ternary complexes by mixing pre-formed PEI complexes with liposomes ( [24,25], Ewe et al, pending revisions), amino acid modification of PEI or the covalent coupling of antibodies for targeted delivery.…”

Section: Introductionmentioning

confidence: 99%

“…Lipopolyplexes containing the low molecular weight PEI F25-LMW and the phospholipid DPPC, with or without different co-lipids, have been described for the delivery of siRNA. They showed very good transfection efficiencies despite strongly reduced surface charges as well as improved biocompatibility and excellent storage stabilities under various conditions [25,32]. Since phospholipids are the main components of cell membranes, they are associated with high biocompatibility and clinically approved for drug delivery [33,34].…”

Section: Introductionmentioning

confidence: 99%

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Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model

Ewe

Höbel

Heine

et al. 2016

Drug Deliv. and Transl. Res.

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The non-viral delivery of small RNA molecules like siRNAs still poses a major bottleneck for their successful application in vivo. This is particularly true with regard to crossing physiological barriers upon systemic administration. We have previously established polyethylenimine (PEI)-based complexes for therapeutic RNA formulation. These nanoplexes mediate full RNA protection against nucleolytic degradation, delivery to target tissues as well as cellular uptake, intracellular release and therapeutic efficacy in preclinical in vivo models. We herein present data on different polyplex modifications for the defined improvement of physicochemical and biological nanoparticle properties and for targeted delivery. (i) By non-covalent modifications of PEI polyplexes with phospholipid liposomes, ternary complexes ("lipopolyplexes") are obtained that combine the favorable features of PEI and lipid systems. Decreased cytotoxicity and highly efficient delivery of siRNA is achieved. Some lipopolyplexes also allow prolonged storage, thus providing formulations with higher stability. (ii) Novel tyrosine modifications of low molecular weight PEI offer further improvement of stability, biocompatibility, and knockdown efficacy of resulting nanoparticles. (iii) For ligand-mediated uptake, the shielding of surface charges is a critical requirement. This is achieved by PEI grafting with polyethylene glycol (PEG), prior to covalent coupling of anti-HER1 antibodies (Erbitux®) as ligand for targeted delivery and uptake. Beyond tumor cell culture, analyses are extended towards tumor slice cultures from tumor xenograft tissues which reflect more realistically the in vivo situation. The determination of siRNA-mediated knockdown of endogenous target genes, i.e., the oncogenic survival factor survivin and the oncogenic receptor tyrosine kinase HER2, reveals nanoparticle penetration and biological efficacy also under intact tissue and stroma conditions.

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Section: Liposome Pei Complex and Lipopolyplex Preparationmentioning

confidence: 99%

Section: Liposome Pei Complex and Lipopolyplex Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model

Ewe

Höbel

Heine

et al. 2016

Drug Deliv. and Transl. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Poly Ethylen Imine (PEI) on the other hand is a proven polymer for gene delivery and is often considered as a gold standard for transfection [14][15][16]. A combination of PEI/nucleic acid polyplexes and liposomes called Lipopolyplexes (LPP) has been proven to increase the efficiency of gene delivery and decrease the toxicity associated with polyethylenimine [17][18][19]. In this study, we present the use of a novel combination of curcumin loaded liposomes and PEI/DNA polyplexes for photochemical internalisation.…”

Section: Introductionmentioning

confidence: 99%

Photo-Enhanced Delivery of Genetic Material Using Curcumin Loaded Composite Nanocarriers

Bakowsky¹

2017

Clin Oncol

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High‐Performance Delivery of a CRISPR Interference System via Lipid‐Polymer Hybrid Nanoparticles Combined with Ultrasound‐Mediated Microbubble Destruction for Tumor‐Specific Gene Repression

Zhu

et al. 2023

Adv Healthcare Materials

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The dCas9-based CRISPR interference (CRISPRi) system efficiently silences genes without causing detectable off-target activity, thus showing great potential for the treatment of cancer at the transcriptional level. However, due to the large size of the commonly used CRISPRi system, effective delivery of the system has been a challenge that hinders its application in the clinic. Herein, a combination of pH-responsive lipid-polymer hybrid nanoparticles (PLPNs) and ultrasound-mediated microbubble destruction (UMMD) is used for the delivery of the CRISPRi system. The core-shell structure of PLPNs can effectively be loaded with the CRISPRi plasmid, and increases the time spent in the circulating in vivo, and "actively target" cancer cells. Moreover, the combination of PLPNs with UMMD achieves a higher cellular uptake of the CRISPRi plasmid in vitro and retention in vivo. Furthermore, when PLPNs loaded with a CRISPRi plasmid that targets microRNA-10b (miR-10b) are used in combination with UMMD, it results in the effective repression of miR-10b in breast cancer, simultaneous disturbance of multiple cell migration and invasion-related signaling pathways, and a significant inhibition of lung metastasis. Thus, the established system presents a versatile, highly efficient, and safe strategy for delivery of the CRISPRi system both in vitro and in vivo.

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Storage stability of optimal liposome–polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery

Cited by 67 publications

References 64 publications

Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model

Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model

Photo-Enhanced Delivery of Genetic Material Using Curcumin Loaded Composite Nanocarriers

High‐Performance Delivery of a CRISPR Interference System via Lipid‐Polymer Hybrid Nanoparticles Combined with Ultrasound‐Mediated Microbubble Destruction for Tumor‐Specific Gene Repression

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