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Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in vitro analysis

2015-02Journal article Restricted access
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dc.contributor.authorGooding, M.
dc.contributor.authorMalhotra, Meenakshi
dc.contributor.authorMcCarthy, D. J.
dc.contributor.authorGodinho, Bruno M. C.
dc.contributor.authorCryan, John F.
dc.contributor.authorDarcy, R.
dc.contributor.authorO’Driscoll, Caitriona M.
dc.date.accessioned2015-03-10T15:24:48Z
dc.date.available2015-03-10T15:24:48Z
dc.date.issued2015-02
dc.description.abstractIn man brain cancer is an aggressive, malignant form of tumour, it is highly infiltrative in nature, is associated with cellular heterogeneity and affects cerebral hemispheres of the brain. Current drug therapies are inadequate and an unmet clinical need exists to develop new improved therapeutics. The ability to silence genes associated with disease progression by using short interfering RNA (siRNA) presents the potential to develop safe and effective therapies. In this work, in order to protect the siRNA from degradation, promote cell specific uptake and enhance gene silencing efficiency, a PEGylated cyclodextrin (CD)-based nanoparticle, tagged with a CNS-targeting peptide derived from the rabies virus glycoprotein (RVG) was formulated and characterized. The modified cyclodextrin derivatives were synthesized and co-formulated to form nanoparticles containing siRNA which were analysed for size, surface charge, stability, cellular uptake and gene-knockdown in brain cancer cells. The results identified an optimised co-formulation prototype at a molar ratio of 1:1.5:0.5 (cationic cyclodextrin:PEGylated cyclodextrin:RVG-tagged PEGylated cyclodextrin) with a size of 281±39.72nm, a surface charge of 26.73±3mV, with efficient cellular uptake and a 27% gene-knockdown ability. This CD-based formulation represents a potential nanocomplex for systemic delivery of siRNA targeting brain cancer.por
dc.identifier.citationGooding M, Malhotra M, McCarthy DJ, Godinho BM, Cryan JF, Darcy R, et al. Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in vitro analysis. Eur J Pharm Sci. 2015;71C:80-92.por
dc.identifier.doi10.1016/j.ejps.2015.02.007
dc.identifier.urihttp://hdl.handle.net/10400.21/4369
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0928098715000573#por
dc.subjectBrain cancerpor
dc.subjectCyclodextrinspor
dc.subjectGene deliverypor
dc.subjectNanoparticlespor
dc.subjectRVGpor
dc.subjectsiRNApor
dc.titleSynthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in vitro analysispor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage92por
oaire.citation.startPage80por
oaire.citation.volume71por
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor

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