The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles
Abstract
The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG(5000)-b-p(HPMAm-lac(2)), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, p<0.01). Duodenal administration of polymeric micelles together with bile acids in bile duct ligated rats fully restored absorption. Dynamic light scattering time series showed a significant and dose dependent rise in micellar size in the presence of bile acids in vitro, indicating the gradual formation of mixed micelles during the first 3 h of incubation. The highest bile acid amounts (11 mM deoxycholic acid and 41 mM taurocholic acid) eventually caused aggregation of the loaded micelles after the formation of mixed micelles. These data suggest that the gastrointestinal absorption of encapsulated vitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.
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Media such as FASSGF, FASSIF, or buffers enriched in bile acids could be employed to simulate gastrointestinal conditions.
“Particularly, media such as the Fasted State Simulated Gastric Fluid (FASSGF) simulating physiological conditions in the stomach at the fasted state, the Fasted State Simulated Intestinal Fluid (FASSIF) reproducing upper intestine conditions or buffers enriched in bile acids could be employed [128,129].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [128]
Other authors determined drug release profiles in buffers reproducing gastro-intestinal tract conditions to examine micelles' attitude to disaggregate or release the cargo when orally administered.
“Other Authors determined drug release profile in buffers reproducing gastro-intestinal tract conditions to examine micelles attitude to disaggregate or release the cargo when orally administered.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [128]
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- Authors
- van Hasselt, P. M., Janssens, G. E. P. J., Slot, T. K., van der Ham, M., Minderhoud, T. C., Talelli, M., Akkermans, L. M., Rijcken, C. J. F., & van Nostrum, C. F.
- Affiliations
- Utrecht University (NL)
- University Medical Center Utrecht (NL)
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 133
- Issue
- 2
- Pages
- 161-168
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2063900272
- Cited by
- 60
- References
- 35
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 7
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- vitamin K, polymeric micelles, bile acids, oral bioavailability, gastrointestinal absorption, bile duct ligation, thermosensitive block copolymers, mixed micelles, micelle aggregation, deoxycholic acid, taurocholate, hydrophobic drug delivery, pinocytosis
- MeSH terms
- Administration, Oral, Animals, Bile Acids and Salts, Bile Ducts, Biological Availability, Drug Carriers, Drug Stability, Hydrogen-Ion Concentration, Intestinal Absorption, Ligation, Light, Male, Micelles, Particle Size, Polyethylene Glycols, Polymers, Polymethacrylic Acids, Scattering, Radiation, Ultrafiltration, Vitamin K, Vitamins, Rats, Wistar, Area Under Curve, Microscopy, Electron, Transmission, Rats
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