Highly mucus permeating and zeta potential changing self-emulsifying drug delivery systems: A potent gene delivery model for causal treatment of cystic fibrosis

Griesser, Janine; Hetényi, Gergely; Federer, Christoph; Steinbring, Christian; Ellemunter, Helmut; Niedermayr, Katharina; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ijpharm.2018.12.048

Cited by 37 publications

(17 citation statements)

References 37 publications

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“…Zeta-potentials of the magnetite and magnetite/silver nanoparticles were measured at different pH values to determine their colloidal stability under different environmental conditions. This is of considerable importance for the development of stable nanovehicles for drug delivery [ 44 ]. Figure 2 B shows the obtained Zeta-potentials in the pH range from 6 to 8.…”

Section: Resultsmentioning

confidence: 99%

“…Also, it shows how both magnetite and magnetite/silver exhibit similar behavior. However, in the case of magnetite/silver, there is a considerable decrease in the absolute value of the Zeta potential, thereby making them less colloidally-stable [ 44 ]. This could be related to the electrical properties and shape of silver [ 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…The magnetite and magnetite/silver nanoparticles show hydrodynamic diameters larger than those observed in the TEM images, as shown in Figure 2 C–E. This could be related to the aggregation of the nanoparticles and their low colloidal stability [ 30 , 44 ]. To avoid aggregation of the nanoparticles, it is possible to use mechanical methods such as sonication or chemical methods such as a suspension in ionic solvents [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

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PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

et al. 2020

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Over the past decade, gene therapies have attracted much attention for the development of treatments for various conditions, including cancer, neurodegenerative diseases, protein deficiencies, and autoimmune disorders. Despite the benefits of this approach, several challenges are yet to be solved to reach clinical implementation. Some of these challenges include low transfection rates, limited stability under physiological conditions, and low specificity towards the target cells. An avenue to overcome such issues is to deliver the therapies with the aid of potent cell-penetrating vectors. Non-viral vectors, such as nanostructured materials, have been successfully tested in drug and gene delivery. Here, we propose the development and in vitro evaluation of a nanostructured cell-penetrating vehicle based on core/shell, magnetite/silver nanoparticles. A subsequent conjugation of a pH-responsive polymer was used to assure that the vehicle can carry and release circular DNA. Additionally, the translocating peptide Buforin II was conjugated with the aid of a polyether amine polymer to facilitate translocation and endosome escape. The obtained nanobioconjugates (magnetite/silver-pDMAEMA-PEA-BUFII) were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope equipped with energy dispersive spectroscopy (SEM+EDS), and transmission electron microscopy (TEM). They were also encapsulated in lecithin liposomes to form magnetoliposomes. The cell viability of Vero cells in the presence of the nanobioconjugates was above 95% and declined to 80% for the magnetoliposomes. The hemolytic tendency of nanobioconjugates and magnetoliposomes was below 10%, while the platelet aggregation approached that of the negative control (i.e., 35%). Cytoplasm coverage values of about 50% for both Vero and neuroblastoma cells confirmed significant cell penetration. Pearson’s correlation coefficients for both cell lines allowed us to estimate 20–40% colocalization of the nanobioconjugates with lysotracker green, which implied high levels of endosomal escape. The developed vehicles were also capable of loading around 16% of the added DNA and releasing such cargo with 8% efficiency. The developed nanoplatform holds a significant promise to enable highly efficient gene therapies as it overcomes some of the major issues associated with their eventual translation to the pre-clinical and clinical scale.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

et al. 2020

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“…Firstly, the cationic lipid stearylamine was incorporated into the nanoparticles, in order to obtain cationic SNs and favor the association of miRNA mimics (SNs-ST). Secondly, we proposed the encapsulation of preformed DOTAP-miRNA lipid complexes (Lpx) into SNs (SNs-Lpx) to provide additional protection for the associated miRNA mimics, following a similar approach to that described for plasmid DNA (pDNA), complexed via hydrophobic ion pairing utilizing surfactants and further incorporated into self-nanoemulsifying drug delivery systems [20,21]. Intracellular delivery, cell transfection, and functional in vitro assays were accomplished to determine the potential of the proposed formulations to develop new oncosuppressor therapies for colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

et al. 2020

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Gene replacement therapy with oncosuppressor microRNAs (miRNAs) is a promising alternative to interfere with cancer progression. However, miRNAs are highly inefficient in a biological environment, hampering a successful translation to clinics. Nanotechnology can tackle this drawback by providing delivery systems able to efficiently deliver them to cancer cells. Thus, the objective of this work was to develop biocompatible nanosystems based on sphingomyelin (SM) for the intracellular delivery of miRNAs to colorectal cancer cells. We pursued two different approaches to select the most appropriate composition for miRNA delivery. On the one hand, we prepared sphingomyelin-based nanosystems (SNs) that incorporate the cationic lipid stearylamine (ST) to support the association of miRNA by the establishment of electrostatic interactions (SNs–ST). On the other hand, the cationic surfactant (DOTAP) was used to preform lipidic complexes with miRNA (Lpx), which were further encapsulated into SNs (SNs-Lpx). Restitution of miRNA145 levels after transfection with SNs-Lpx was related to the strongest anticancer effect in terms of tumor proliferation, colony forming, and migration capacity assays. Altogether, our results suggest that SNs have the potential for miRNA delivery to develop innovative anticancer therapies.

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“…Zpc-SEDDS are loaded with phosphorylated ligands bearing amino groups and possess an overall negative charge in the intestinal lumen facilitating their mucus diffusion. Once Zpc-SEDDS reach the epithelium the phosphate groups are cleaved by intestinal alkaline phosphatase (AP) with a shift in zeta potential toward positive values, that reduces back diffusion of the formulations and promotes their uptake [51]. In vivo data provided evidence of the efficacy of zeta potential changing systems in improving oral bioavailability of peptides [52].…”

Section: Impact Of the Findingsmentioning

confidence: 99%

Impact of bile salts and a medium chain fatty acid on the physical properties of self-emulsifying drug delivery systems

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Steinbring

Friedl

et al. 2020

Drug Development and Industrial Pharmacy

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Highly mucus permeating and zeta potential changing self-emulsifying drug delivery systems: A potent gene delivery model for causal treatment of cystic fibrosis

Cited by 37 publications

References 37 publications

PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

Impact of bile salts and a medium chain fatty acid on the physical properties of self-emulsifying drug delivery systems

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