Visualization and analysis of superparamagnetic iron oxide nanoparticles in the inner ear by light microscopy and energy filtered TEM

Thaler, Marlene; Roy, Soumen; Fornara, Andrea; Bitsche, Mario; Qin, Jian; Muhammed, Mamoun; Salvenmoser, Willi; Rieger, Gunde; Fischer, Anneliese Schrott; Glueckert, Rudolf

doi:10.1016/j.nano.2010.11.005

Cited by 26 publications

(16 citation statements)

References 23 publications

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“…Although sustained release delivery systems have been studied extensively in other routes of administrations, these systems have only been recently investigated for inner ear delivery 2 . In vitro methods to study inner ear delivery systems are also limited with only a handful of reports in the literature of methods such as drug release in containers 15,33 , excised temporal bones and organotypic explant cultures 34 , cell culture on membrane inserts in multiple well plates 35 , cell layer membrane model 36 and conventional Franz diffusion cells 37 . A standard in vitro testing method using diffusion cells to evaluate drug formulations such as sustained delivery systems for the inner ear is not available.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

Liu

Feng

Tolia

et al. 2013

Drug Development and Industrial Pharmacy

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A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions.

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Section: Discussionmentioning

confidence: 99%

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

Liu

Feng

Tolia

et al. 2013

Drug Development and Industrial Pharmacy

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“…0.2μm). 321 Furthermore, TEM offers additional tools such as electron beam diffraction 299 and elemental analysis 322, 323 that can be used to differentiate iron oxides encapsulated in ferritin from the crystalline and superparamagnetic IONPs encapsulated in the lysosomes of liver and spleen macrophages; thus, TEM can provide detailed information about the pharmacokinetic and degradation pathways of IONPs. 78 It should be noted, however, that TEM needs electron transparent samples requiring costly and elaborate preparation procedures.…”

Section: Methods For Determining Pharamacokinetics and Biodistribumentioning

confidence: 99%

In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles

et al. 2015

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Iron oxide nanoparticles (IONPs) have been extensively used during the last two decades, either as effective bio-imaging contrast agents or as carriers of biomolecules such as drugs, nucleic acids and peptides for controlled delivery to specific organs and tissues. Most of these novel applications require elaborate tuning of the physiochemical and surface properties of the IONPs. As new IONPs designs are envisioned, synergistic consideration of the body's innate biological barriers against the administered nanoparticles and the short and long-term side effects of the IONPs become even more essential. There are several important criteria (e.g. size and size-distribution, charge, coating molecules, and plasma protein adsorption) that can be effectively tuned to control the in vivo pharmacokinetics and biodistribution of the IONPs. This paper reviews these crucial parameters, in light of biological barriers in the body, and the latest IONPs design strategies used to overcome them. A careful review of the long-term biodistribution and side effects of the IONPs in relation to nanoparticle design is also given. While the discussions presented in this review are specific to IONPs, some of the information can be readily applied to other nanoparticle systems, such as gold, silver, silica, calcium phosphates and various polymers.

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“…Cochleae were than incubated in 1% OsO 4 for 1 h at 4°C in 0.05 M cacodylate buffer. Specimen were then dehydrated in an ascending EtOH series and embedded in Epon 812 (Electron Microscopy Science, Hatfield, UK, 14120) as described elsewhere (Thaler et al, 2011 ; Pritz et al, 2013a ).…”

Section: Methodsmentioning

confidence: 99%

Nanoparticle mediated drug delivery of rolipram to tyrosine kinase B positive cells in the inner ear with targeting peptides and agonistic antibodies

Glueckert

Pritz

Roy

et al. 2015

Front. Aging Neurosci.

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Aim: Systemic pharmacotherapies have limitation due to blood-labyrinth barrier, so local delivery via the round window membrane opens a path for effective treatment. Multifunctional nanoparticle (NP)-mediated cell specific drug delivery may enhance efficacy and reduce side effects. Different NPs with ligands to target TrkB receptor were tested. Distribution, uptake mechanisms, trafficking, and bioefficacy of drug release of rolipram loaded NPs were evaluated.Methods: We tested lipid based nanocapsules (LNCs), Quantum Dot, silica NPs with surface modification by peptides mimicking TrkB or TrkB activating antibodies. Bioefficacy of drug release was tested with rolipram loaded LNCs to prevent cisplatin-induced apoptosis. We established different cell culture models with SH-SY-5Y and inner ear derived cell lines and used neonatal and adult mouse explants. Uptake and trafficking was evaluated with FACS and confocal as well as transmission electron microscopy.Results: Plain NPs show some selectivity in uptake related to the in vitro system properties, carrier material, and NP size. Some peptide ligands provide enhanced targeted uptake to neuronal cells but failed to show this in cell cultures. Agonistic antibodies linked to silica NPs showed TrkB activation and enhanced binding to inner ear derived cells. Rolipram loaded LNCs proved as effective carriers to prevent cisplatin-induced apoptosis.Discussion: Most NPs with targeting ligands showed limited effects to enhance uptake. NP aggregation and unspecific binding may change uptake mechanisms and impair endocytosis by an overload of NPs. This may affect survival signaling. NPs with antibodies activate survival signaling and show effective binding to TrkB positive cells but needs further optimization for specific internalization. Bioefficiacy of rolipram release confirms LNCs as encouraging vectors for drug delivery of lipophilic agents to the inner ear with ideal release characteristics independent of endocytosis.

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Visualization and analysis of superparamagnetic iron oxide nanoparticles in the inner ear by light microscopy and energy filtered TEM

Cited by 26 publications

References 23 publications

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles

Nanoparticle mediated drug delivery of rolipram to tyrosine kinase B positive cells in the inner ear with targeting peptides and agonistic antibodies

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