Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We have studied sterically stabilized micelles (SSMs) of self-assembled DSPE–PEG2000 in pure water and isotonic HEPES-buffered saline solution. The observed SSM sizes of 2–15 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration of DSPE–PEG2000 is 10 times higher in water than in buffer, and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we performed atomistic molecular dynamics simulations of solvated SSMs. Our modeling revealed that the observed assemblies have very different aggregation numbers (N(agg) ≈ 90 in saline solution and N(agg)< 8 in water) because of very different screening of their charged PO4(–) groups. We also demonstrate that the micelle cores can inflate and their coronas can fluctuate strongly, thus allowing storage and delivery of molecules with different chemistries.

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-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. Discussion: 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. 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.