Self-nanoemulsifying drug delivery systems as novel approach for pDNA drug delivery

Int J Pharm. 2015 Jun 20;487(1-2):25-31. doi: 10.1016/j.ijpharm.2015.03.064. Epub 2015 Mar 31.

Abstract

It was the aim of this study to investigate a novel strategy for oral gene delivery utilizing a self-nanoemulsifying drug delivery system (SNEDDS). After hydrophobic ion pairing a plasmid was incorporated into SNEDDS. The mean droplet size of resulting nanoemulsions was determined to be between 45.8 and 47.5 nm. A concentration dependent cytotoxicity of the formulations was found on HEK-293 cells via MTT assay. Degradation studies via DNase I showed that incorporation into SNEDDS led to significantly, up to 8-fold prolonged resistant time against enzymatic digestion compared to naked pDNA and pDNA-lipid complexes. Transfection studies carried out revealed a significantly improved transfection compared to naked pDNA. Further, no decrease in transfection efficiency compared to transfection using Lipofectin(®) transfection reagent was observed.

Keywords: 1-Hexadecylpyridin-1-ium;chloride (PubChem CID: 31239); 2,3-Bis[(Z)-octadec-9-enoxy]propyl-trimethylazanium;chloride (PubChem CID: 6438350); Cremophor-EL (PubChem CID 5849927); Dodecyl(trimethyl)azanium;bromide (PubChem CID: 14249); Gene delivery; Hexadecyl(trimethyl)azanium;bromide (PubChem CID: 5974); Hydrophobic ion pairing; Nonviral vector; SNEDDS; [3-[2-Aminoethoxy(hydroxy)phosphoryl]oxy-2-[(Z)-octadec-9-enoyl]oxypropyl] (Z)-octadec-9-enoate (PubChem CID: 6437392).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • DNA / administration & dosage*
  • DNA / therapeutic use
  • Deoxyribonuclease I / chemistry
  • Drug Delivery Systems
  • Emulsions
  • Genetic Therapy / methods*
  • Green Fluorescent Proteins
  • HEK293 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Indicators and Reagents
  • Lipids / chemistry
  • Nanostructures / chemistry*
  • Particle Size
  • Plasmids / genetics
  • Transfection

Substances

  • Emulsions
  • Indicators and Reagents
  • Lipids
  • Green Fluorescent Proteins
  • DNA
  • Deoxyribonuclease I