Ultrasound-enhanced transfection activity of HPMA-stabilized DNA polyplexes with prolonged plasma circulation
- 2 September 2005
- journal article
- Published by Elsevier BV in Journal of Controlled Release
- Vol. 106 (3), 416-427
- https://doi.org/10.1016/j.jconrel.2005.05.002
Abstract
Cancer gene therapy would greatly benefit from the possibility to deliver therapeutic genes via tumor-targeted systemic intravenous delivery. The main objective of this study was to determine biophysical, transfection, and pharmacokinetic properties of DNA complexes with reducible polycations that are reversibly stabilized by surface coating with multivalent HPMA copolymers. The specific goals were to evaluate compatibility of these polyplexes with extended plasma circulation, molecular targeting, and ultrasound-enhanced transfection activity. It was demonstrated that using polyplexes based on reducible polycations allows increasing transfection activity and preserving extended plasma circulation half-life observed for control polyplexes based on non-reducible polycations. In addition, the reversibly stabilized polyplexes were compatible with both molecular targeting using protein ligands as well as physical targeting using ultrasound-directed cavitation in vitro. As such, the described gene delivery vectors have the potential to permit efficient systemic delivery of therapeutic genes targeted by a local focused ultrasound treatment.Keywords
This publication has 40 references indexed in Scilit:
- Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimineJournal of Controlled Release, 2003
- Prospects for cationic polymers in gene and oligonucleotide therapy against cancerAdvanced Drug Delivery Reviews, 2002
- Influence of Physicochemical Properties on Pharmacokinetics of Non-viral Vectors for Gene DeliveryJournal of Drug Targeting, 2002
- Development of Long-circulating Polyelectrolyte Complexes for Systemic Delivery of GenesJournal of Drug Targeting, 2002
- Development of gene drug delivery systems based on pharmacokinetic studiesEuropean Journal of Pharmaceutical Sciences, 2001
- The fate of poly(2-dimethyl amino ethyl)methacrylate-based polyplexes after intravenous administrationInternational Journal of Pharmaceutics, 2001
- Steric Stabilization of poly-l-Lysine/DNA Complexes by the Covalent Attachment of Semitelechelic poly[N-(2-Hydroxypropyl)methacrylamide]Bioconjugate Chemistry, 2000
- Hepatocyte-targeted in vivo gene expression by intravenous injection of plasmid DNA complexed with synthetic multi-functional gene delivery systemGene Therapy, 2000
- Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomesGene Therapy, 2000
- Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene deliveryGene Therapy, 1999