Polymyxin B self-associated with phospholipid nanomicelles

Kenneth S. Brandenburg, Israel Rubinstein, Ruxana T. Sadikot, Hayat Önyüksel

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Context: 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. Materials and methods: PXB and SSM (15 nm) composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N [methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) 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. Discussion: PXB's self-association with SSM resulted in mitigation of the in vitro antibacterial activity. This phenomenon could be attributed, in part, to PEG2000 hindering electrostatic interactions between cationic PXB and anionic bacterial cell wall. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)654-660
Number of pages7
JournalPharmaceutical Development and Technology
Volume17
Issue number6
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • Antibacterial
  • Drug delivery
  • Gram-negative bacteria
  • Nanobiotechnology
  • Nanomedicine
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Pharmaceutical Science

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