Intrapericardial administration of novel DNA formulations based on thermosensitive Poloxamer 407 gel

• Published in: International journal of pharmaceutics Vol. 331; no. 2; pp. 220 - 223
• Main Authors: Roques, C., Salmon, A., Fiszman, M.Y., Fattal, E., Fromes, Y.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.2007; Elsevier
• Subjects: Biological and medical sciences; Cardiomyopathies - drug therapy; DNA - administration & dosage; Drug Carriers - chemistry; Drug Carriers - toxicity; Gels; Gene therapy; General pharmacology; Infusions, Parenteral; Intrapericardial administration; Medical sciences; Pericardium; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmid DNA; Poloxamer - therapeutic use; Poloxamer - toxicity; Polyethyleneimine; Polyethyleneimine - toxicity; Surface-Active Agents; Temperature; Thermosensitive gel; Polyethyleneimine; Intrapericardial administration; Gene therapy; Plasmid DNA; Thermosensitive gel; Pharmaceutical technology; Vehicle(excipient); Laxative; Thermal labile product; Colloidal gel; Plasmid; DNA; Formulation; Poloxamer; Dosage form
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.11.056

Inherited cardiopathies are leading to life-threatening conditions such as heart failure. Moreover, treatments currently available fail in altering the cardiac phenotype. Thus, gene therapy appears as an attracting alternative to conventional treatments. However, gene delivery remains a major hurdle in achieving this goal. To obtain regional delivery of plasmid DNA, intrapericardial administration seems to be an interesting approach. In order to improve retention time at the site of injection, formulations based on a thermosensitive gel of Poloxamer 407 were assessed. Protection and condensation of plasmid DNA was initially performed through complexation with polyethyleneimine (PEI), a widely used polymer. Characterization of the size and zeta potential of the complexes suggested interactions between the polyplexes and the Poloxamer gel through significant increase of the size of the polyplexes and shielding of the surface charges. In vivo evaluation has highlighted the toxicity of PEI/DNA polyplexes toward the myocardium. However, feasibility of intrapericardial injection of Poloxamer based formulations as well as their very low toxicity has been established.