Parameters affecting organization and transfection efficiency of amphiphilic copolymers/DNA carriers.
Amphiphilic block copolymers are attracting increasing interest in the field of gene therapy, especially for transfection of striated muscles. However, little is known about the parameters affecting their transfection efficiency in vivo. These copolymers can self-assemble as micelles in certain conditions. Since micellization strongly depends on the temperature and ionic content of the preparation medium, the present paper aimed at investigating the influence of these parameters in the context of gene delivery. We first assessed the micellization of pluronic L64 and tetronic 304 at various temperatures in water, saline or Tyrode's salts solution. Pluronic L64 can form micelles at temperatures above 37 degrees C in water or at 37 degrees C in the Tyrode's salts solution, in the range of concentration investigated. For tetronic 304, CMC was found to be far below the concentrations used to transfer DNA. Pluronic L64 interacted with DNA only in the presence of micelles. Moreover, in vivo evaluation demonstrated that significantly improved transfection efficiency was obtained at 37 degrees C in Tyrode's salts solution for pluronic L64 based formulations, compared to 4 degrees C and 20 degrees C. Such differences were not recorded with tetronic 304. Finally, optimized formulations of both tetronic 304 and pluronic L64 were able to mediate efficient transfection in dystrophic muscles.
Univ Paris Sud 11, UMR CNRS 8612, France; CNRS, Châtenay-Malabry, F-92290, France.
Caroline
C
Roques
Kawthar
K
Bouchemal
Gilles
G
Ponchel
Yves
Y
Fromes
Elias
E
Fattal
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002151:Calorimetry; D006224:Cricetinae; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D015870:Gene Expression; D008823:Micelles; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011108:Polymers / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D013696:Temperature; D017186:Titrimetry; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D013501:Surface-Active Agents; D004247:DNA; D001616:beta-Galactosidase