About: Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium

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About: Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium
Creator	Avasarala, Sumant Brewer, Daniel Grashik, Jordan Conti, Denise Da Rocha, Sandro
Source	Medline; PMC
abstract	[Image: see text] Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)–siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA–G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after siRNA has been exposed to the propellant environment.
has issue date	2014-04-28(xsd:dateTime)
bibo:doi	10.1021/mp4006358
bibo:pmid	24811243
has license	no-cc
sha1sum (hex)	af13aa4011a57e2670ce8204394e3a11f173109d
schema:url	https://doi.org/10.1021/mp4006358
resource representing a document's title	Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium
has PubMed Central identifier	PMC4051247
has PubMed identifier	24811243
schema:publication	Mol Pharm
resource representing a document's body	covid:af13aa4011a57e2670ce8204394e3a11f173109d#body_text
is schema:about of	named entity 'based' named entity 'cystic fibrosis' named entity 'aerosol' named entity 'pulmonary' named entity 'A549' named entity 'eGFP' named entity 'epithelial' named entity 'propellant' named entity 'deep' named entity 'lung' named entity 'siRNA' named entity 'Formulations' covid:arg/af13aa4011a57e2670ce8204394e3a11f173109d named entity 'lung' named entity 'hydrofluoroalkane' named entity 'administration' named entity 'siRNA' named entity 'ability' named entity 'water-soluble' named entity 'statistically significant' named entity 'siRNA' named entity 'metering valves' named entity 'One-Way ANOVA' named entity 'siRNA' named entity 'siRNA' named entity 'cytotoxicity' named entity 'siRNA' named entity 'aerosol spray' named entity 'mannitol' named entity 'siRNA' named entity 'A549 cells' named entity 'lungs' named entity 'dendrimers' named entity 'One-Way ANOVA' named entity 'GSD' named entity 'oligomer' named entity 'time' named entity 'number' named entity 'biodegradable' named entity 'devices' named entity 'lung' named entity 'dendrimer' named entity 'deep' named entity 'siRNA' named entity 'Dendrimer' named entity 'lungs' named entity 'siRNA' named entity 'alveolar epithelial cells' named entity 'lung' named entity 'amine' named entity 'inhalation' named entity 'lung cancer' named entity 'A549' named entity 'oligomer' named entity 'lung' named entity 'gene' named entity 'aerosol' named entity 'amidoamine' named entity 'biodegradable' named entity 'siRNA' named entity 'siRNA' named entity 'aerosol' named entity 'lung' named entity 'siRNA' named entity 'gene knockdown' named entity 'gene expression' named entity 'spray drying' named entity 'alveolar epithelium' named entity 'spray drying' named entity 'eGFP' named entity 'tertiary amines' named entity 'A549 cells' named entity 'exogenous' named entity 'morphology' named entity 'One-Way ANOVA' named entity 'aerosol' named entity 'transfected'

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