title: Polymyxin B self-associated with phospholipid nanomicelles.
abstract: BACKGROUND
  Although Polymyxin B (PXB) is an effective antibiotic for Gram-negative bacterial infections, clinical use is hampered by toxicity and protein binding, which may be overcome by delivering PXB using a safe nanocarrier.
  
  
  OBJECTIVE
  To determine whether PXB self-associates with long-circulating biocompatible/biodegradable PEGylated phospholipid nanomicelles (SSM) and change the PXB in vitro bioactivity.
  
  
  METHODS
  PXB and SSM (15 nm) composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N [methoxy(polyethylene glycol)-2000] (DSPE-PEG(2000)) were prepared in 10 mM HEPES-buffered saline. Interactions between PXB and SSM were determined by dynamic light scattering and fluorescence spectroscopy. Anti-infective effects of PXB-SSM were tested against Pseudomonas aeruginosa strain PA01 in vitro.
  
  
  RESULTS
  Approximately four PXB molecules self-associated with each SSM. However, significant decrease in P. aeruginosa killing was observed with PXB-SSM relative to PXB alone (P < 0.05). Empty SSM had no significant effect on bacterial growth.
  
  
  CONCLUSIONS
  PXB's self-association with SSM resulted in mitigation of the in vitro antibacterial activity. This phenomenon could be attributed, in part, to PEG(2000) hindering electrostatic interactions between cationic PXB and anionic bacterial cell wall.
  
  
  CONCLUSIONS
  PXB association with SSM formed a stable nanomedicine, resulting in decreased bioactivity of the drug in vitro. Effectiveness of this nanomedicine in vivo is yet to be studied.
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, IL, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Brandenburg
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Ruxana T
authors.initials: RT
authors.lastname: Sadikot
authors.forename: Hayat
authors.initials: H
authors.lastname: Önyüksel
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D008823:Micelles; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011112:Polymyxin B / Q000737:chemistry* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D004337:Drug Carriers; D008823:Micelles; D010743:Phospholipids; D011092:Polyethylene Glycols; D011112:Polymyxin B