Alice Ng Jie Ying,Yang Fei Tan,Yee Shan Wong,Subbu Venkatraman
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引用次数: 0
Abstract
BACKGROUND
Sustained siRNA release from nanocarriers is difficult to achieve inside the cell after entry: typically, all nanocarriers exhibit burst release of the cargo into the cytoplasm.
RESEARCH DESIGN AND METHODS
Layer by layer (LbL) nanoparticles (NPs) can be constructed so that they escape endosomes intact, and subsequently exhibit sustained release of the cargo. Our work quantifies intra-cellular siRNA release from multilayered NPs, evaluates mechanism behind the sustained release, and optimizes the duration of release.
RESULTS
Intra-cellular studies showed that nanoparticles developed with 4 layers of polyL-arginine, alternated with 3 layers of siRNA layers was able to elicit effective and prolonged SPARC knockdown activity over 21 days with a single dose treatment. For the first time, we have quantified the amounts of released siRNA in the cytoplasm and the amount of siRNA remaining inside the nanoparticles at each timepoint. Furthermore, we have correlated the amount of released siRNA within cells by LbL NPs to the cellular knockdown efficiency of multilayered delivery system.
CONCLUSIONS
This methodology may provide an excellent screening tool for assessing the duration of gene silencing by various nanocarrier formulations.
期刊介绍:
Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.