title: Freeze drying of peptide drugs self-associated with long-circulating, biocompatible and biodegradable sterically stabilized phospholipid nanomicelles.
abstract: The purpose of this study was to determine optimal lipid concentration range for lyophilization of sterically stabilized phospholipid nanomicelles (SSM) and the freeze drying feasibility of self-associated therapeutic peptide-SSM assemblies. SSM at 5-20 mM 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE-PEG(2000)) were analyzed for particle size and viscosity before and after freeze drying which showed no significant changes (p>0.05). However, a steep increase in viscosity was seen for SSM above 15 mM phospholipid implying micelle-micelle interaction. Greater shrinkage of lyophilized cakes was observed below 10 mM phospholipid while they were more fibrous above 15 mM. Therefore, 10-15 mM DSPE-PEG(2000) was chosen as the optimal phospholipid concentration for lyophilized SSM. When vasoactive intestinal peptide (VIP), glucagon-like peptide 1 (GLP-1) or gastric inhibitory peptide (GIP) (each, 67 microM) was added to SSM (10mM), formulations showed no significant change in particle size, peptide fluorescence and peptide alpha-helicity before and after lyophilization. In conclusion, we found that peptide drug-SSM interactions are conserved during lyophilization.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612-7231, USA.
authors.forename: Sok Bee
authors.initials: SB
authors.lastname: Lim
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyüksel
mesh_terms: D004355:Drug Stability; D005612:Freeze Drying; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D008823:Micelles; D053758:Nanoparticles; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry; D014783:Viscosity
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D008823:Micelles; D010455:Peptides; D010714:Phosphatidylethanolamines; D014660:Vasoactive Intestinal Peptide; D011092:Polyethylene Glycols; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1