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Small nanosized poly(vinyl benzyl trimethylammonium chloride) based polyplexes for siRNA delivery.

Abstract
The success of siRNA gene therapy requires the availability of safe and efficient delivery systems. In the present study, we investigated poly(vinyl benzyl trimethylammonium chloride) (PVTC) and its block copolymer with poly(oligo(ethyleneglycol) methacrylate) (POEGMA) as delivery vector for siRNA. Small polyplexes ranging from 8 to 25nm in diameter were formed in aqueous solution by spontaneous self-assembly of both the homopolymer and block copolymer with siRNA and the formed particles were stable at physiological ionic strength. It was shown that when human ovarian adenocarcinoma cells were transfected, siRNA polyplexes based on PVTC (40kDa) and PVTC-POEGMA-4 (PP4, 34kDa) efficiently induced luciferase gene silencing to the same extent as the formulation based on a commercial lipid (Lipofectamine®) (∼80%), and showed higher gene silencing than the linear polyethylenimine formulation linear polyethylenimine (∼35%). Importantly, the POEGMA block polymers displayed a significantly lower cytotoxicity as compared to L-pEI. siRNA polyplexes based on the block polymers displayed high cellular uptake resulting in ∼50% silencing of luciferase expression also in the presence of serum. These results demonstrate that PVTC-based polymers are promising siRNA delivery vectors.
AuthorsBo Lou, Nataliia Beztsinna, Grigoris Mountrichas, Joep B van den Dikkenberg, Stergios Pispas, Wim E Hennink
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 525 Issue 2 Pg. 388-396 (Jun 20 2017) ISSN: 1873-3476 [Electronic] Netherlands
PMID28336456 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier B.V. All rights reserved.
Chemical References
  • Polymers
  • Polystyrenes
  • Quaternary Ammonium Compounds
  • RNA, Small Interfering
  • poly(vinylbenzyltrimethylammonium chloride)
Topics
  • Adenocarcinoma (genetics, therapy)
  • Cell Line, Tumor
  • Gene Silencing
  • Genetic Therapy (methods)
  • Humans
  • Polymers
  • Polystyrenes (chemistry)
  • Quaternary Ammonium Compounds (chemistry)
  • RNA, Small Interfering (administration & dosage)
  • Transfection

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