Effects of PAMAM dendrimers in the mouse brain after a single intranasal instillation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56159 | GEO | 2014/03/26
SECONDARY ACCESSION(S): PRJNA242608
REPOSITORIES: GEO
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Project description:The in vivo effects of nasal exposure to polyamidoamine (PAMAM) dendrimers on their effects on gene expression in the mouse brain. A single dose of PAMAM dendrimers or saline (control) was intranasally administered to 8-week old male BALB/c mice. PAMAM-induced gene expression in the olfactory bulb, hippocampus, and cerebral cortex was measured at 24 hours after exposure to doses of 0, 0.15 mg/kg b.w. Pooled RNA from six independent experiments were analyzed at each time.
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Project description:Polyamidoamine (PAMAM) dendrimers have been investigated for the development of engineered nanomaterial drug delivery systems and other industrial uses. However, the major concern for their potential adverse effects on human neural progenitor cells remains unclear. In the present study, we employed human neural progenitor cells (hNPCs) to study the effects of G4-PAMAM dendrimers on neuronal differentiation.
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Project description:Polyamidoamine (PAMAM) dendrimers have been investigated for the development of engineered nanomaterial drug delivery systems and other industrial uses. However, the major concern for their potential adverse effects on human neural progenitor cells remains unclear. In the present study, we employed human neural progenitor cells (hNPCs) to study the effects of G4-PAMAM dendrimers on neuronal differentiation. Neurospheres were treated with PAMAM dendrimer-NH2 (10 M-NM-<g/mL) for 72 h. Four neurospheres from the treatment and control groups were pooled together, and RNAs were isolated from each group.
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Project description:Transcriptomic response of zebrafish embryos to Polyamidoamine (PAMAM) dendrimers
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Project description:This study evaluated transcriptional effects of nanomaterials that have been proposed for use as platforms for drug delivery. We tested SiO2 that had been surface modified to have a positive zetapotential of different geometries as well PAMAM dendrimers with different surface charges. We tested these materials on human aortic endothelial cells (HAECs) since we were interested in determining if there was a toxicogenomic response in endothelial cells that may come into contact with drug delivery nanoplatforms. The most pronounced transcriptional response resulted from the SiO2 treatement - the most prevelant responses were cell cycle, lipid metabolism and pro-inflammatory responses - with fewer responses from the PAMAM dendrimers. The lipid metabolism responses may relate to teh positive surface character as this response was not observed in the G3.5-COOH dendrimers. Indeed, the G3.5-COOH dendrimers were non-toxic and did not demonstrate any consistent transcriptional response.
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Project description:We are presenting here the application of toxicogenomics to perform the evaluation of toxic effects of two polyamidoamine dendrimers (Generation3 and Generation4) on the developing zebrafish embryo. They are nanomaterials of special concern under the toxicological point of view because of their relatively high solubility in water and bioavailability. Zebrafish embryo toxicity assays (zFET) showed that G3 was more toxic to zebrafish than G4, and that both compounds were several orders of magnitude more toxic than other carbonaceous nanomaterials, like carbon fullerenes or nanotubes. The results suggest a variety of MoA for different dendrimers, probably related to the nature and number of the chemical groups attached to their surface. They also confirm the relatively high bioavailability of these compounds, a key factor for the assessment of the risk associated to their use and release into the environment. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process and also in the nervous system development. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of generations of dendrimers studied. Two different treatments were performed in this study. Zebrafish fertlized eggs were exposed to PAMAM dendrimer G3 and G4 during 48h. 3 biological replicates per studied dendrimer are included such as each control sample.
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Project description:Corneal alkali burns cause persistent inflammation, leading to corneal vascularization and fibrosis, which severely impair vision. Here, we developed a temporary adhesive silk-based patch to capture and remove inflammatory mediators from the ocular surface. The patch utilizes photocrosslinkable silk for mechanical support, chitosan as the adhesive, hyaluronan for lubrication, and polyamidoamine (PAMAM) dendrimers with heparin to enhance adsorption. After water annealing, the patch exhibited excellent transparency, mechanical strength, and resistance to swelling, remaining attached to the rat ocular surface for 3–5 days. Adsorption tests confirmed that the patch effectively captured small-molecule dyes, proteins, and free DNA. In the rat corneal alkali burn model, imaging and histological evaluations showed significant reductions in vascularization and fibrosis after 3 days of treatment, along with improved corneal transparency. RNA sequencing revealed that patch treatment effectively inhibited the PI3K–AKT inflammatory pathway. This inflammation-removing patch represents an innovative treatment for corneal alkali burns with significant clinical potential.
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Project description:Effects of PAMAM dendrimers in the mouse brain after a single intranasal instillation
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