title: Lyophilization of cholesterol-free PEGylated liposomes and its impact on drug loading by passive equilibration.
abstract: The obstacles in translating liposome formulations into marketable products could be attributed to their physical instabilities upon long-term storage as aqueous dispersions. Lyophilization is the most commonly used technique to improve physical stability of liposomes. The development of stable, lyophilized liposomes is focused primarily on the cholesterol-containing liposomes or pure phosphatidylcholine-based liposomes, with minimal studies on cholesterol-free, pegylated (CF-PEG) liposomes which have emerged as an important class of liposome drug carriers. Hence, it is our interest to investigate the effect of lyophilization on CF-PEG liposomes, and specifically, on drug loading via the passive equilibration method. Three different sugar cryoprotectants were used at two different sugar-to-lipid molar ratios (S/L). Our results demonstrated that CF-PEG liposomes lyophilized with sucrose at S/L=5:1 yielded the best cryoprotective effect, as characterized by size, polydispersity indices, and microscopic examination upon liposome reconstitution. The lyophilized liposomes had low water content of 2.59 ± 0.18%. Of note, lyophilized CF-PEG liposomes exhibited two-fold increase in drug content when carboplatin was loaded via the passive equilibration method, and the in vitro drug release profile of these liposomes were not different from that of the non-lyophilized counterparts. Taken together, we envisioned that a stable, lyophilized empty CF-PEG liposome system could be coupled to hydrophilic drug loading via the passive equilibration method to produce a liposomal drug kit product.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Anumita
authors.initials: A
authors.lastname: Chaudhury
authors.forename: Surajit
authors.initials: S
authors.lastname: Das
authors.forename: Ronald F S
authors.initials: RF
authors.lastname: Lee
authors.forename: Kuan-Boone
authors.initials: KB
authors.lastname: Tan
authors.forename: Wai-Kiong
authors.initials: WK
authors.lastname: Ng
authors.forename: Reginald B H
authors.initials: RB
authors.lastname: Tan
authors.forename: Gigi N C
authors.initials: GN
authors.lastname: Chiu
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D016190:Carboplatin / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003451:Cryoprotective Agents / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D005612:Freeze Drying; D005947:Glucose / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013395:Sucrose / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D014199:Trehalose / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003451:Cryoprotective Agents; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; D013395:Sucrose; D014199:Trehalose; D016190:Carboplatin; C010942:1,2-distearoyllecithin; D005947:Glucose