Preparation of polyethyleneimine incorporated poly(d,l-lactide-co-glycolide) nanoparticles by spontaneous emulsion diffusion method for small interfering RNA delivery

Haliza Katas, Erdal Cevher, H. Oya Alpar

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Gene therapy based on small interfering RNA (siRNA) has emerged as an exciting new therapeutic approach. However, insufficient cellular uptake and poor stability have limited its usefulness. Polyethyleneimine (PEI) has been extensively studied as a vector for nucleic acids and incorporation of PEI into poly(d,l-lactide-co-glycolide) (PLGA) particles has been shown to be useful in the development of gene delivery. PEI was incorporated into the PLGA particles by spontaneous modified emulsification diffusion method. Incorporation of PEI into PLGA particles with the PLGA to PEI weight ratio 29:1 was found to produce spherical and positively charged nanoparticles where type of polymer, type and concentration of surfactant could affect their physical properties. Particle size of around 100 nm was obtained when 5% (m/v) PVA was used as a stabiliser. PLGA-PEI nanoparticles were able to completely bind siRNA at N/P ratio 20:1 and to provide protection for siRNA against nuclease degradation. In vitro cell culture studies subsequently revealed that PLGA-PEI nanoparticles with adsorbed siRNA could efficiently silence the targeted gene in mammalian cells, better than PEI alone, with acceptable cell viability. PLGA-PEI nanoparticles have been found to be superior to its cationising parent compound; PEI polymer. Crown

Original languageEnglish
Pages (from-to)144-154
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume369
Issue number1-2
DOIs
Publication statusPublished - 18 Mar 2009

Fingerprint

Polyethyleneimine
Emulsions
Nanoparticles
Small Interfering RNA
Polymers
dilactide
Ribonucleases
polylactic acid-polyglycolic acid copolymer
Crowns
Particle Size
Surface-Active Agents
Genetic Therapy
Nucleic Acids
Genes
Cell Survival
Cell Culture Techniques

Keywords

  • Gene silencing
  • Nanoparticles
  • Poly(d,l-lactide-co-glycolide)
  • Polyethyleneimine
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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abstract = "Gene therapy based on small interfering RNA (siRNA) has emerged as an exciting new therapeutic approach. However, insufficient cellular uptake and poor stability have limited its usefulness. Polyethyleneimine (PEI) has been extensively studied as a vector for nucleic acids and incorporation of PEI into poly(d,l-lactide-co-glycolide) (PLGA) particles has been shown to be useful in the development of gene delivery. PEI was incorporated into the PLGA particles by spontaneous modified emulsification diffusion method. Incorporation of PEI into PLGA particles with the PLGA to PEI weight ratio 29:1 was found to produce spherical and positively charged nanoparticles where type of polymer, type and concentration of surfactant could affect their physical properties. Particle size of around 100 nm was obtained when 5{\%} (m/v) PVA was used as a stabiliser. PLGA-PEI nanoparticles were able to completely bind siRNA at N/P ratio 20:1 and to provide protection for siRNA against nuclease degradation. In vitro cell culture studies subsequently revealed that PLGA-PEI nanoparticles with adsorbed siRNA could efficiently silence the targeted gene in mammalian cells, better than PEI alone, with acceptable cell viability. PLGA-PEI nanoparticles have been found to be superior to its cationising parent compound; PEI polymer. Crown",
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