title: Effect of solubilizing agents on mupirocin loading into and release from PEGylated nanoliposomes.
abstract: Mupirocin was identified by quantitative structure property relationship models as a good candidate for remote liposomal loading. Mupirocin is an antibiotic that is currently restricted to topical administration because of rapid hydrolysis in vivo to its inactive metabolite. Formulating mupirocin in PEGylated nanoliposomes may potentially expand its use to parenteral administration by protecting it from degradation in the circulation and target it (by the enhanced permeability effect) to the infected tissue. Mupirocin is slightly soluble in aqueous medium and its solubility can be increased using solubilizing agents. The effect of the solubilizing agents on mupirocin remote loading was studied when the solubilizing agents were added to the drug loading solution. Propylene glycol was found to increase mupirocin loading, whereas polyethylene glycol 400 showed no effect. Hydroxypropyl-β-cyclodextrin (HPCD) showed a concentration-dependent effect on mupirocin loading; using the optimal HPCD concentration increased loading, but higher concentrations inhibited it. The inclusion of HPCD in the liposome aqueous phase while forming the liposomes resulted in increased drug loading and substantially inhibited drug release in serum.
authors.affiliation: Laboratory of Membrane and Liposome Research, Department of Biochemistry, IMRIC, The Hebrew University - Hadassah Medical School, Jerusalem, Israel; Molecular Modeling and Drug Design Laboratory, The Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ahuva
authors.initials: A
authors.lastname: Cern
authors.affiliation: Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Nativ-Roth
authors.affiliation: Molecular Modeling and Drug Design Laboratory, The Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Amiram
authors.initials: A
authors.lastname: Goldblum
authors.affiliation: Laboratory of Membrane and Liposome Research, Department of Biochemistry, IMRIC, The Hebrew University - Hadassah Medical School, Jerusalem, Israel. Electronic address: chezyb@ekmd.huji.ac.il.
authors.forename: Yechezkel
authors.initials: Y
authors.lastname: Barenholz
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000085:Acetates / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D017610:Calcium Compounds / Q000737:chemistry; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D015195:Drug Design; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D008081:Liposomes; D016712:Mupirocin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D019946:Propylene Glycol / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000085:Acetates; D000900:Anti-Bacterial Agents; D017610:Calcium Compounds; D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D016712:Mupirocin; C120662:calcium acetate
keywords: computer-aided drug design; excipients; formulation; liposomes; nanoparticles; solubility