Interaction of liposomes with bile salts investigated by asymmetric flow field-flow fractionation (AF4): A novel approach for stability assessment of oral drug carriers
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For oral drug delivery the stability of liposomes against intestinal bile salts is of key importance. Here, asymmetric flow field-flow fractionation (AF4) coupled to multi-angle laser light scattering (MALLS) and a differential refractive index (dRI) detector was employed to monitor structural re-arrangement of liposomes upon exposure to the model bile salt taurocholate. For comparison, a conventional stability assay was employed using a hydrophilic marker and size exclusion chromatography (SEC) to separate released from liposome-entrapped dye. Calcein-containing liposomes with and without cholesterol were compared in terms of their in vitro stability upon exposure to bile salts by separating liposomes from co-existing colloidal species emerging after stress test using AF4/MALLS/dRI. Dynamic light scattering (DLS) was utilized in parallel. Our AF4/MALLS/dRI results suggested that exposure of egg-phospholipid liposomes to bile salts at physiological concentrations led to the formation of two new species of colloidal associates, likely (mixed) micelles. Subjecting cholesterol-containing liposomes to the same bile media did not lead to any new colloidal structures, indicating increased stability of these liposomes. Our SEC-based release assay largely confirmed these findings, indicating that AF4/MALLS/dRI is a suitable technique for prediction of in vitro oral stability of liposomal formulations. Moreover, the powerful AF4/MALLS/dRI technique appears promising to improve the understanding of the underlying mechanisms during bile salt-induced liposomal breakdown.
Original language | English |
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Article number | 106384 |
Journal | European Journal of Pharmaceutical Sciences |
Volume | 182 |
Number of pages | 10 |
ISSN | 0928-0987 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Funding Information:
The authors would like to acknowledge Assoc. Prof. Judith Kuntsche from SDU for her AF4/MALLS/dRI-expertise and guidance. This study was funded by a Phospholipid Research Center grant to AHT (ATR-2019–074/1–1) and received support from the Nordic University Hub project (#85352, MB) (NordicPOP, Patient Oriented Products).
- Asymmetric flow field-flow fractionation, Bile salt, Dynamic light scattering, Liposome, Oral administration, Size exclusion chromatography
Research areas
ID: 336123837