title: Physico-chemical characterisation of cationic DOTAP liposomes as drug delivery system for a hydrophilic decapeptide before and after freeze-drying.
abstract: In the present study, positively charged 1,2-dioleoyloxy-3-trimethylammoniumpropane (DOTAP) liposomes as a delivery system for a hydrophilic decapeptide were developed. The main objective was the preparation of a stable, highly loaded, lyophilised formulation to yield the basis for an acceptable shelf life. The influences of addition of cholesterol, pH value, amounts of lipid and peptide, type and amount of sugar-based cryoprotective agent (trehalose and sucrose), and time point for cryoprotector addition as well as the freeze-drying process parameters were investigated. The collapse temperatures of the liposome dispersions in the presence of the disaccharides trehalose and sucrose were determined using a freeze-drying microscope (Lyostat 2). The liposome morphology before freeze-drying was determined by transmission electron microscopy (TEM). The evidence of intact liposomes after freeze-drying was shown by scanning electron microscope (SEM) imaging. In summary, this study demonstrated the successful development of DOTAP liposomes including their lyophilisation as a drug delivery system for small hydrophilic peptides.
authors: Merck Serono, Formulation and Process Development, Darmstadt, Germany. alena.wieber@merckgroup.com
authors: Alena
authors: A
authors: Wieber
authors: Torsten
authors: T
authors: Selzer
authors: Jörg
authors: J
authors: Kreuter
mesh_terms: D002412:Cations; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
chemical_list: D002412:Cations; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D009842:Oligopeptides; D000644:Quaternary Ammonium Compounds; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane