Interaction of liposomes with bile salts investigated by asymmetric flow field-flow fractionation (AF4):A novel approach for stability assessment of oral drug carriers

Autor: Mette Sloth Bohsen, Sofie Tandrup Tychsen, Ali Abdul Hussein Kadhim, Holger Grohganz, Alexander H. Treusch, Martin Brandl
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Bohsen, M S, Tychsen, S T, Kadhim, A A H, Grohganz, H, Treusch, A H & Brandl, M 2023, ' Interaction of liposomes with bile salts investigated by asymmetric flow field-flow fractionation (AF4) : A novel approach for stability assessment of oral drug carriers ', European Journal of Pharmaceutical Sciences, vol. 182, 106384 . https://doi.org/10.1016/j.ejps.2023.106384
DOI: 10.1016/j.ejps.2023.106384
Popis: 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.
Databáze: OpenAIRE