2. Academic Validation
  3. Limited cellular uptake of liposomes: Might thiolated phospholipids hold the key?

Limited cellular uptake of liposomes: Might thiolated phospholipids hold the key?

  • Int J Pharm. 2024 Dec 25;667(Pt A):124812. doi: 10.1016/j.ijpharm.2024.124812.
Daniel Stengel 1,  Zeliha Duygu Özdal 2,  Martyna Truszkowska 1,  Ahmad Saleh 3,  Anna Seybold 4,  Andreas Bernkop-Schnürch 5
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria.
  • 2 Department of Pharmaceutical Technology, Faculty of Pharmacy, Erzincan Binali Yildirim University, Erzincan 24100, Turkey.
  • 3 Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria; Department of Pharmacy, Universitas Mandala Waluya, A.H.Nasution, Kendari, 93231, Southeast Sulawesi, Republic of Indonesia.
  • 4 Department of Zoology, University of Innsbruck, 6020 Innsbruck, Austria.
  • 5 Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria. Electronic address: [email protected].
PMID: 39424086 DOI: 10.1016/j.ijpharm.2024.124812
Abstract

Aim: It was the aim of this study to evaluate the impact of surface thiolation on cellular uptake of liposomes.

Methods: Liposomes were prepared via the thin lipid film method, incorporating Cholesterol, dipalmitoylphosphatidylcholin (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol). The characterization of liposomes included size, polydispersity index, surface morphology, zeta potential and stability in simulated gastric and intestinal fluid. Hemocompatibility and cytotoxicity of liposomes were investigated. Cellular uptake studies were performed on Caco-2, HEK, HeLa and SW620 cells, involving both quantitative analysis through flow cytometry and qualitative evaluation via confocal microscopy. Additionally, we investigated the impact of an oxidizing agent on thiol-dependent uptake.

Results: Non-thiolated and thiolated liposomes exhibited a size of 149 nm to 274 nm and a PDI between 0.3 and 0.45. Liposomes were stable in simulated intestinal and gastric fluid. Hemocompatibility studies and cytocompatibility studies of liposomes showed negligible toxic effects of liposomes. Cellular uptake of thiolated liposomes was 1.8-, 2.1-, 5.4- and 1.4-fold enhanced in comparison to non-thiolated liposomes on Caco-2, HEK, HELA and SW620 cells, respectively. The results were qualitatively verified by confocal microscopy. Thiol dependent uptake was influenced by oxidizing agents on HeLa cells.

Conclusion: Surface thiolation represents a promising approach to enhance cellular uptake of liposomes.

Keywords

Cellular uptake; Confocal microscopy; Cytocompatibility; Hemocompatibility; Liposomes; Thiol-dependent uptake.

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