Construction of Bio-conjugated nano-vesicles using non-ionic surfactants for targeted drug delivery: A computational supported experimental study

Introduction

Targeted delivery of drugs to the brain is a complicated activity. This complication is caused by the blood–brain barrier (BBB). Interestingly, there are various transporters on the surface of the BBB that are naturally used for the transportation of specific compounds. A practical approach for brain drug delivery is targeting these transporters with appropriate biomolecules. Large Amino Acid Transporter 1 (LAT1) and Glucose transporter 1 (GLUT1) are two essential transporters on the surface of the BBB that transport amino acids and carbohydrates, respectively.

Methods

In this study, we evaluated the binding affinity of various biomolecules such as amino acids and carbohydrates against their related transporters by conducting molecular docking study. The biomolecules with the highest binding affinity were selected for conjugation to the niosomes. After the conjugation of biomolecules to cetyl alcohol, the bio-conjugated vesicles were constructed with a non-ionic surfactant (Span60) and cholesterol by the thin-film hydration method. The size distribution of formulations was measured with Dynamic Light Scattering. The niosomal formulations were treated on the HUVEC cells and the cellular uptake of the niosomes was assessed by fluorescent microscopy.

Highlights

• The binding affinity of various biomolecules to their related transporters was evaluated using computational approaches.
• The appropriate carbohydrates and amino acids were selected and conjugated to the vesicles.
• The trehalose-conjugated niosomes exhibited considerable cellular uptake in HUVEC cells.

Results

Trehalose and glucose showed the highest binding affinity to GLUT1 (-7.787 and −5.715 kcal/mol, respectively), and threonine and glutamine showed the highest binding affinity to LAT1 (-4.532 and −5.946, respectively). Trehalose-conjugated niosomes with a size distribution of 60 nm represent the highest cellular uptake in HUVEC cells.

Conclusion

Computational approaches are practical methods for selecting appropriate targeting agents. In addition, trehalose is a potential agent for bio-conjugation and can improve the transport of the niosomes through the BBB.

Read more

Alireza Poustforoosh, Sanaz Farmarz, Mohammad Hadi Nematollahi, Hassan Hashemipour, Abbas Pardakhty, Construction of Bio-conjugated nano-vesicles using non-ionic surfactants for targeted drug delivery: A computational supported experimental study, Journal of Molecular Liquids, Volume 367, Part B, 2022, 120588, ISSN 0167-7322, https://doi.org/10.1016/j.molliq.2022.120588.