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

• Published in: European journal of pharmaceutical sciences 2023-03, Vol.182, p.106384-106384, Article 106384
• Main Authors: Bohsen, Mette Sloth, Tychsen, Sofie Tandrup, Kadhim, Ali Abdul Hussein, Grohganz, Holger, Treusch, Alexander H., Brandl, Martin
• Format: Article
• Language: English
• Subjects: Asymmetric flow field-flow fractionation; Bile Acids and Salts; Bile salt; Drug Carriers; Drug Delivery Systems; Dynamic light scattering; Liposome; Liposomes - chemistry; Micelles; Oral administration; Particle Size; Size exclusion chromatography
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2023.106384

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. [Display omitted]