Rational evaluation of the utilization of PEG-PEI copolymers for the facilitation of silica nanoparticulate systems in biomedical applications

Karaman, Didem Şen; Gulin-Sarfraz, Tina; Hedström, Gun; Duchanoy, Alain; Eklund, Patrik; Rosenholm, Jessica M.

doi:10.1016/j.jcis.2013.11.080

Cited by 37 publications

(36 citation statements)

References 36 publications

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“…In addition, rod-shaped particles have in certain cases proven to be more efficient in permeability studies [2, 3], which is why we set out to investigate whether we could detect any favorable effects related to aspect ratio in our case as well. The synthesized particles were further coated with in-house produced PEG-PEI copolymers [17] which could, if desired, be further attached to biomolecular moieties. All four particle designs are depicted in Fig 1.…”

Section: Resultsmentioning

confidence: 99%

“…The ζ-potentials at neutral pH confirmed that both particles in question were comparable to pure silica in terms of net surface charge (despite the addition of small amounts of aminosilane for the covalent attachment of the fluorescent label) and thus applicable for electrostatic coating of the produced PEG-PEI copolymer. In this specific copolymer construct, the cationic PEI part is used to anchor strongly to the negatively charged silica surface, whereas the PEG chains are expected to ‘stick out’ from the particle surface and thus impart the particle system with a steric stabilization component [17]. Further, PEG is probably the most commonly employed polymer coating for nanomedical systems especially with in vivo prospects.…”

Section: Resultsmentioning

confidence: 99%

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Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

et al. 2016

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Drug delivery into the brain is impeded by the blood-brain-barrier (BBB) that filters out the vast majority of drugs after systemic administration. In this work, we assessed the transport, uptake and cytotoxicity of promising drug nanocarriers, mesoporous silica nanoparticles (MSNs), in in vitro models of the BBB. RBE4 rat brain endothelial cells and Madin-Darby canine kidney epithelial cells, strain II, were used as BBB models. We studied spherical and rod-shaped MSNs with the following modifications: bare MSNs and MSNs coated with a poly(ethylene glycol)-poly(ethylene imine) (PEG-PEI) block copolymer. In transport studies, MSNs showed low permeability, whereas the results of the cellular uptake studies suggest robust uptake of PEG-PEI-coated MSNs. None of the MSNs showed significant toxic effects in the cell viability studies. While the shape effect was detectable but small, especially in the real-time surface plasmon resonance measurements, coating with PEG-PEI copolymers clearly facilitated the uptake of MSNs. Finally, we evaluated the in vivo detectability of one of the best candidates, i.e. the copolymer-coated rod-shaped MSNs, by two-photon in vivo imaging in the brain vasculature. The particles were clearly detectable after intravenous injection and caused no damage to the BBB. Thus, when properly designed, the uptake of MSNs could potentially be utilized for the delivery of drugs into the brain via transcellular transport.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

et al. 2016

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“…A very similar behavior related to the reorganization of copolymers on the silica nanoparticles was also observed in one of our previous study. 32 Moreover, we checked the ζ-Potential of chitosan coated MSPs over a day, we didn't notice any significant changes in the ζ-potential values. To the best our knowledge, once the physical adsorption of macromolecules (such proteins, polymers) occurs on the particles surfaces, they are difficult to release without harsh pH changes of the environment or strong mechanical treatments.…”

Section: Characterization Of Msps and Release Of Ag + From Mspsmentioning

confidence: 95%

Shape engineering boosts antibacterial activity of chitosan coated mesoporous silica nanoparticle doped with silver: a mechanistic investigation

et al. 2016

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In this study mesoporous silica nanoparticles (MSPs) of different size and shape were developed, and their surface coatings altered to study their differential effect in enhancing the antibacterial activity. In brief, MSPs with three different aspect ratios 1, 2 and 4 were prepared, doped with silver ions and finally coated with the polymer chitosan. Both Gram-positive and Gram-negative bacteria were treated with the MSPs. Results indicated that silver ion doped and chitosan coated MSPs with the aspect ratio 4 (Cht/MSP4:Ag + ) has the highest antimicrobial activity among the prepared series. Further studies revealed that Cht/MSP4:Ag + was most effective against Escherichia coli (E.coli) and least effective against Vibrio cholerae (V.cholerae). To investigate the detailed inhibition mechanism of the MSPs, the interaction of the nanoparticles with E.coli membranes and its intracellular DNA was assessed using various spectroscopic and imaging-based techniques. Furthermore to increase the efficiency of the MSP combinatorial antibacterial strategy was also explored -nanoparticles in combination with kanamycin (antibiotic) was treated against Vibrio Cholerae (V. cholerae). Toxicity screening of these MSPs was conducted against Caco-2 cells, and the results show that the dose used for antibacterial screening is below the limit of toxicity threshold. Our findings show that both shape and surface engineering contributes positively towards bacteria killing, and the newly developed silver ion-doped and chitosan-coated MSP has good potential as an antimicrobial nanomaterial.

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“…34 Both plain MSNs and PEI-MSNs were further functionalized with PEG utilizing the primary amine groups of either the aminosilane (for plain MSNs) or terminal ends of PEI (for PEI-MSNs). Particles (50 mg) were dispersed in chloroform and were allowed to react with 12.5 mg hexamethylene diisocyanate (HMDI)-activated methoxy-PEG (mPEG) 29,35 (Supplementary materials) in the presence of 5 μL N,N-diisopropylethylamine (DIPEA) overnight at 60°C under reflux. After the reaction, the particles were washed with ethanol and vacuum-dried to yield PEG-MSNs and PEG-PEI-MSNs.…”

Section: Experimental Synthesis Functionalization and Bioconjugatiomentioning

confidence: 99%

“…28 In our approach, PEGylation was achieved by attaching PEG either directly to the particle surface or via a grafted PEI layer. 29 Further, folic acid (FA) was conjugated to the MSNs as a potential affinity ligand.…”

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confidence: 99%

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

Desai¹,

Prabhakar²,

Mamaeva³

et al. 2016

IJN

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Targeted delivery of drugs is required to efficiently treat intestinal diseases such as colon cancer and inflammation. Nanoparticles could overcome challenges in oral administration caused by drug degradation at low pH and poor permeability through mucus layers, and offer targeted delivery to diseased cells in order to avoid adverse effects. Here, we demonstrate that functionalization of mesoporous silica nanoparticles (MSNs) by polymeric surface grafts facilitates transport through the mucosal barrier and enhances cellular internalization. MSNs functionalized with poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and the targeting ligand folic acid in different combinations are internalized by epithelial cells in vitro and in vivo after oral gavage. Functionalized MSNs loaded with γ-secretase inhibitors of the Notch pathway, a key regulator of intestinal progenitor cells, colon cancer, and inflammation, demonstrated enhanced intestinal goblet cell differentiation as compared to free drug. Drug-loaded MSNs thus remained intact in vivo, further confirmed by exposure to simulated gastric and intestinal fluids in vitro. Drug targeting and efficacy in different parts of the intestine could be tuned by MSN surface modifications, with PEI coating exhibiting higher affinity for the small intestine and PEI–PEG coating for the colon. The data highlight the potential of nanomedicines for targeted delivery to distinct regions of the tissue for strict therapeutic control.

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Rational evaluation of the utilization of PEG-PEI copolymers for the facilitation of silica nanoparticulate systems in biomedical applications

Cited by 37 publications

References 36 publications

Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

Shape engineering boosts antibacterial activity of chitosan coated mesoporous silica nanoparticle doped with silver: a mechanistic investigation

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

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