Toward understanding polymer micelle stability: Density ultracentrifugation offers insight into polymer micelle stability in human fluids
Open accessAbstract
Micelles, as a class of drug delivery systems, are underrepresented among United States Food and Drug Administration approved drugs. A lack of clinical translation of these systems may be due to, in part, to a lack of understanding of micelle interactions with biologic fluids following injection. Despite the limited clinical translation, micelles remain an active area of research focus and pre-clinical development. The goal of the present study was to examine the stability of amphiphilic block copolymer micelles in biologic fluids to identify the properties and components of biologic fluids that influence micelle stability. Micelle stability, measured via Förster resonance energy transfer-based fluorescent spectrometry, was complemented with density ultracentrifugation to reveal the colocalized, or dissociated, state of the dye cargo after exposure to human biologic fluids. Polymeric micelles composed of poly(ethylene glycol-block-caprolactone) (mPEG-CL) and poly(ethylene glycol-block-lactide) (mPEG-LA) were unstable in fetal bovine serum, human serum and synovial fluid, with varying levels of instability observed in ascites and pleural fluid. All polymeric micelles exhibited stability in cerebrospinal fluid, highlighting the potential for local cerebro-spinal administration of micelles. Interestingly, mPEG 2.2k-CL 3.1k and mPEG 2k-LA 2.7k micelles favored dissolution whereas mPEG 5.4k-LA 28.5k micelles favored stability. Taken together, our data offers both quantitative and qualitative evidence for micelle stability within human biologic fluids and offers evidence of polymer micelle instability in biologic fluids that is not explained by either total protein content or total unsaturated lipid content. The results help to identify potential sites for local delivery where stability is maintained.
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Data obtained with AF4 in terms of micelles integrity have been correlated with the pharmacokinetic profile, allowing prediction of the stability or instability of drug-loaded micelles after intravenous administration.
“Very recently, the data obtained with AF4 in terms of micelles integrity have been correlated with the pharmacokinetic profile, allowing to predict the stability or instability of drug loaded micelles after i.v.administration [242].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [242]
The Abstract describes micelle-stability measurements using FRET spectrometry and density ultracentrifugation, not AF4. The Discussion says the results are expected to be predictive of in vivo stability but notes limits to extrapolating from the fluids studied. Searches for AF4 and a correlation with a pharmacokinetic profile found no passage establishing the claimed prediction after intravenous administration. (LLM, conf=0.76)
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Ghezzi, M., Pescina, S., Padula, C., Santi, P., Del Favero, E., Cantù, L., & Nicoli, S. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.02.031 · Cited by 1,135 · see citing works
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- Authors
- Langridge, T. D., & Gemeinhart, R. A.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Gemeinhart, Richard A.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 319
- Pages
- 157-167
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC6958513
- OpenAlex
- W2996855738
- Cited by
- 51
- References
- 69
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6 · 2023: 11 · 2022: 6 · 2021: 7 · 2020: 4
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Research Resources
- National Institute of Biomedical Imaging and Bioengineering
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Chemistry › Organic Chemistry › Surfactants and Colloidal Systems
- Keywords
- polymeric micelles, micelle stability, amphiphilic block copolymers, fetal bovine serum, synovial fluid, ascites, pleural fluid, cerebrospinal fluid, local drug delivery, fluorescence resonance energy transfer, micelle dissociation
- MeSH terms
- Drug Carriers, Humans, Micelles, Polyesters, Polyethylene Glycols, Polymers, Ultracentrifugation, Drug Delivery Systems
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