title: Encapsulation enhancement and stabilization of insulin in cationic liposomes.
abstract: The purpose of this study was to enhance encapsulation efficiency and sustained-release delivery for parenteral administration of a protein drug. To reduce the administration frequency of protein drugs, it is necessary to develop sustained delivery systems. In this study, protein drug-loaded cationic liposomes were formulated with dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), dioleoyl-3-trimethylammonium-propane (DOTAP), and cholesterol (CH) at a molar ratio of DOPE/DOTAP/CH of 2/1.5/2. Five mol% of distearoylphosphatidyl ethanolamine polyethylene glycol (DSPE-PEG) was added prior to encapsulation of the drug into liposomes. Insulin was chosen as a model protein drug and encapsulation efficiency was evaluated in various liposomes with and without DSPE-PEG. Scanning electron microscopy was used to examine the insulin-loaded cationic liposomes. Structural analysis was performed using spectropolarimetry. Additionally, the stability and cytotoxicity of insulin-loaded cationic liposomes were evaluated. Liposomes coated with DSPE-PEG showed higher insulin encapsulation efficiency than did those without DSPE-PEG, but not significantly. Moreover, among the liposomes coated with DSPE-PEG, those hydrated with 10% sucrose showed higher encapsulation efficiency than did liposomes hydrated in either phosphate-buffered saline or 5% dextrose. In vitro release of insulin was prolonged by cationic liposomes. Our findings suggest that cationic liposomes may be a potential sustained-release delivery system for parenteral administration of protein and peptide drugs to prolong efficacy and improve bioavailability.
authors.affiliation: College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Soon Gil
authors.initials: SG
authors.lastname: Choi
authors.forename: Enkhzaya
authors.initials: E
authors.lastname: Davaa
authors.forename: Jeong-Sook
authors.initials: JS
authors.lastname: Park
mesh_terms: D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004355:Drug Stability; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D008081:Liposomes; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties
chemical_list: D002412:Cations; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes