title: Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes.
abstract: The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.
authors.forename: Vinayagam
authors.initials: V
authors.lastname: Kannan
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.|b Plough Center for Sterile Drug Delivery, The University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Balabathula
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.
authors.forename: Murali K
authors.initials: MK
authors.lastname: Divi
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.|b Plough Center for Sterile Drug Delivery, The University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Thoma
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.
authors.forename: George C
authors.initials: GC
authors.lastname: Wood
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D008081:Liposomes; D017239:Paclitaxel / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D017239:Paclitaxel
keywords: Cancer chemotherapy; drug–lipid ratio; long circulatory; nanotechnology