title: Highly loaded nanoparticulate carrier using an hydrophobic antisense oligonucleotide complex.
abstract: Antisense oligonucleotides, and particularly those with phosphorothioate backbones, have emerged as potential gene specific therapeutic agents and are currently undergoing evaluation in clinical trials for a variety of diseases. In the area of HIV-1 therapeutics, targeting of oligonucleotides to infected cells, such as macrophages, would be highly desirable. The present study was designed to prepare and characterize oligonucleotide-loaded nanoparticles for this purpose. Due to their hydrophilic characteristics, oligonucleotides are difficult to entrap in polymeric particles. Here, the oligonucleotides were first complexed with cetyltrimethylammonium bromide. The oligonucleotide-loaded nanoparticles were prepared by the emulsification-diffusion method and subsequently purified. In comparison with previous studies, a high oligonucleotide-loading was achieved; 2.5, 5 and 10% oligonucleotide loading were assessed. If the initial oligonucleotide content was 4%, this method produced a final oligonucleotide loading of 1.9% with an entrapment efficiency of 47%. The integrity of the oligonucleotide and of the polymer, in the final freeze-dried product, was retained.
authors.affiliation: School of Pharmacy, University of Geneva, quai E.-Ansermet CH-1211, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Berton
authors.forename: E
authors.initials: E
authors.lastname: Allémann
authors.forename: C A
authors.initials: CA
authors.lastname: Stein
authors.forename: R
authors.initials: R
authors.lastname: Gurny
mesh_terms: D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry*; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000302:isolation & purification; D010316:Particle Size; D010757:Phosphorous Acids / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D002593:Cetrimonium Compounds; D004655:Emulsions; D016376:Oligonucleotides, Antisense; D010757:Phosphorous Acids; D011108:Polymers; D000077286:Cetrimonium