Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.21/4369
Título: Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in vitro analysis
Autor: Gooding, M.
Malhotra, Meenakshi
McCarthy, D. J.
Godinho, Bruno M. C.
Cryan, John F.
Darcy, R.
O’Driscoll, Caitriona M.
Palavras-chave: Brain cancer
Cyclodextrins
Gene delivery
Nanoparticles
RVG
siRNA
Data: Fev-2015
Editora: Elsevier
Citação: Gooding 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.
Resumo: In 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.
Peer review: yes
URI: http://hdl.handle.net/10400.21/4369
DOI: 10.1016/j.ejps.2015.02.007
Versão do Editor: http://www.sciencedirect.com/science/article/pii/S0928098715000573#
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