Compositional inhomogeneity of drug delivery liposomes quantified at the single liposome level

Thomas Lars Andresen, Jannik Bruun Larsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Liposomes are the most used drug delivery vehicle and their therapeutic function is closely linked to their lipid composition. Since most liposome characterization is done using bulk techniques, providing only ensemble averages, the lipid composition of all liposomes within the same formulation are typically assumed to be identical. Here we image individual liposomes using confocal microscopy to quantify that liposomal drug delivery formulations, including multiple component mixtures mimicking Doxil, display more than 10-fold variation in their relative lipid composition. Since liposome function is tightly regulated by the physicochemical properties bestowed by the lipid composition, such significant variations could render only a fraction of liposomes therapeutically active. Additionally, we quantified how this degree of compositional inhomogeneity was modulated by liposome preparation method, the saturation state of the membrane lipid, and whether anti-fouling polyethylene glycol (PEG) conjugated lipids were added to the initial lipid mix or inserted after liposome formation. We believe the insights into the factors governing the degree of inhomogeneity offers the possibility for producing more uniform liposomal drug delivery systems, potentially increasing their therapeutic efficacy.
Original languageEnglish
JournalActa Biomaterialia
Pages (from-to)207-214
Publication statusPublished - 2020


  • Biomaterial composition
  • Liposomal drug delivery systems
  • Single liposome measurements
  • Quantitative fluorescence microscopy
  • Compositional inhomogeneity


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