Protamine sulfate/poly(L-aspartic acid) polyionic complexes self-assembled via electrostatic attractions for combined delivery of drug and gene

Biomaterials. 2009 Feb;30(6):1246-53. doi: 10.1016/j.biomaterials.2008.11.002. Epub 2008 Nov 28.

Abstract

In this study, a series of self-assembled polyionic complexes (PICs) were prepared via electrostatic attraction between protamine sulfate (PS) and poly(L-aspartic acid) (PASP) or doxorubicin (DOX)-conjugated PASP (DOX-PASP). The size of the PICs measured by Nano-ZS ZEN3600 was around 200-300 nm at different weight ratios of PS/PASP. Transmission electron microscopy (TEM) showed that PS/PASP PICs displayed a regular spherical shape and no aggregation was observed. The cytotoxicity study indicated that the PICs did not exhibit apparent cytotoxicity in comparison with that of 25 kDa polyethylenimine (PEI). Gel retardation assay indicated that the PICs were able to bind DNA completely when weight ratio of PS/PASP was higher than 2:1. Luciferase assay and green fluorescent protein (GFP) detection were used to confirm that the PICs could be used as efficient non-viral gene vectors and they exhibited comparable transfection efficiency with the one of 25 kDa PEI. Furthermore, confocal laser scanning microscopy as well as suppression activity of DOX-conjugated PICs (DOX-PICs) showed that they could quickly release the loaded DOX into HeLa cells, indicating that PICs can be also used as carriers for combined delivery of drug and gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • DNA / ultrastructure
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems*
  • Electrophoresis, Agar Gel
  • Gene Transfer Techniques*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Luciferases / metabolism
  • Magnetic Resonance Spectroscopy
  • Microscopy, Electron, Transmission
  • Molecular Weight
  • Particle Size
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protamines / chemistry
  • Protamines / pharmacology*
  • Static Electricity
  • Transfection

Substances

  • Peptides
  • Protamines
  • Green Fluorescent Proteins
  • polyaspartate
  • Doxorubicin
  • DNA
  • Luciferases