Design, synthesis, and physico-chemical interactions of bile acid derived dimeric phospholipid amphiphiles with model membranes.
Understanding of amphiphile-membrane interactions is crucial in design and development of novel amphiphiles for drug delivery, gene therapy, and biomedical applications. Structure and physico-chemical properties of amphiphiles determine their interactions with biomembranes thereby influencing their drug delivery efficacies. Here, we unravel the interactions of bile acid derived dimeric phospholipid amphiphiles with model membranes using Laurdan-based hydration, DPH-based membrane fluidity, and differential scanning calorimetry studies. We synthesized three dimeric bile acid amphiphiles where lithocholic acid, deoxycholic acid, and cholic acid are conjugated to cholic acid phospholipid using click chemistry. Interactions of these dimeric amphiphiles with model membranes showed that these amphiphiles form different structural assemblies and molecular packing in model membranes depending on the number and position of free hydroxyl groups on bile acids. We discovered that cholic acid-cholic acid dimeric phospholipid form self-assembled aggregates in model membranes without changing membrane fluidity; whereas cholic acid-deoxycholic acid derived amphiphile induces membranes fluidity and hydration of model membranes.
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, 180 Udyog Vihar, Phase I, Gurgaon 122016, Haryana, India; Manipal University, Manipal, India.
Sandeep
S
Kumar
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, 180 Udyog Vihar, Phase I, Gurgaon 122016, Haryana, India.
Priyanshu
P
Bhargava
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, 180 Udyog Vihar, Phase I, Gurgaon 122016, Haryana, India; Manipal University, Manipal, India.
Vedagopuram
V
Sreekanth
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, 180 Udyog Vihar, Phase I, Gurgaon 122016, Haryana, India. Electronic address: bajaj@rcb.res.in.
Avinash
A
Bajaj
D001647:Bile Acids and Salts / Q000737:chemistry*; D019281:Dimerization; D008081:Liposomes / Q000737:chemistry*; D008560:Membrane Fluidity; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
D001647:Bile Acids and Salts; D008081:Liposomes; D010743:Phospholipids; D013501:Surface-Active Agents
Bile acids; Liposomes; Membrane interactions; Phospholipids