Direct comparison of standard transmission electron microscopy and cryogenic-TEM in imaging nanocrystals inside liposomes
Open accessAbstract
The use of electron microscopy techniques in the understanding of shape and size of nanoparticles are commonly applied to drug nanotechnology, but the type of microscopy and suitability for the particles of interest can have a significant impact on the result. The size and shape of the nanoparticles are crucial in clinical applications; however, direct comparison of the results from standard transmission electron microscopy (TEM) and cryo-TEM have rarely been reported. As a useful case for comparison, liposomal drug nanocrystals are studied here. In this study, the effect of thawing temperature on the size and shape of the ciprofloxacin nanocrystals was determined. A quantitative standard TEM assay was developed to allow for high-throughput particle size analysis. These results were compared to size and shape information obtained using the cryo-TEM method. The results showed broad agreement between the two TEM methods and that ciprofloxacin nanocrystals formed shorter and thinner crystals inside the liposomes at higher thawing temperatures. The results provide confidence in the use of standard TEM to determine the size and shape distribution of solid nanoparticles (in this case, encapsulated inside liposomes) from aqueous media without fear of sample preparation altering the conclusions.
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- Authors
- Li, T., Nowell, C. J., Cipolla, D., Rades, T., & Boyd, B. J.
- Affiliations
- Monash University (AU)
- Insmed (United States) (US)
- University of Copenhagen (DK)
- Corresponding author
- Boyd, Ben J.
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-02-27
- Volume
- 16
- Issue
- 4
- Pages
- 1775-1781
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2917201626
- Cited by
- 57
- References
- 37
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 14 · 2023: 9 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 1
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- green
- research.monash.edu
- Licence
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (acceptedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Australian Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- ciprofloxacin, cryo-TEM, nanoparticle size and shape, particle size measurement, sample preparation artifacts, liposomes
- MeSH terms
- Ciprofloxacin, Doxorubicin, Liposomes, Cryoelectron Microscopy, Microscopy, Electron, Transmission, Nanoparticles, Molecular Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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