A new delivery system for antisense therapy: PLGA microspheres encapsulating oligonucleotide/polyethyleneimine solid complexes.
Microspheres for the controlled release of an antisense oligonucleotide against the Transforming growth factor beta(1) were designed. Free oligonucleotide or its solid complexes with polyethylenimine (PEI) at different nitrogen/phosphate (N/P) ratios, were encapsulated within poly(lactide-co-glycolide) (PLGA) microspheres prepared by the multiple emulsion-solvent evaporation technique. The encapsulation of the oligonucleotide in form of solid complexes, the N/P ratio, as well as the PLGA type affected microspheres characteristics in term of loading, morphology, oligonucleotide distribution inside matrix and in vitro release profile. The designed microspheres allow the encapsulation and slow release of oligonucleotide/PEI solid complexes that should be effectively internalized inside cells.
De Rosa
Giuseppe
G
Faculté de Pharmacie, Université Paris-Sud UMR CNRS 8612, Group of Drug targeting and delivery of poorly stable compounds, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
Bochot
Amélie
A
Quaglia
Fabiana
F
Besnard
Madeleine
M
Fattal
Elias
E
D000906:Antibodies / Q000737:chemistry / Q000378:metabolism; D001672:Biocompatible Materials; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry* / Q000145:classification; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009584:Nitrogen / Q000737:chemistry / Q000493:pharmacokinetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000145:classification; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000145:classification; D013501:Surface-Active Agents; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism
D000906:Antibodies; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D016376:Oligonucleotides, Antisense; D010710:Phosphates; D011108:Polymers; D013501:Surface-Active Agents; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D009584:Nitrogen