TIFR
Department of Chemical Sciences
School of Natural Sciences

January 25, 2021 at 4.00 pm (via Zoom)

Title :

Studies on Interaction of Peptides and Polymers with Phospholipid Bilayer

Abstract :

In this seminar, I’ll discuss my doctoral research on interaction of peptides and polymers with liposomes for drug delivery applications. Our work has technological potential in the area of drug delivery. But it can also serve as a model system for understanding how the membrane properties change due to interaction with drug delivery cargoes, drug molecules, peptides, and polymers.

Low endosomal escape efficiency of liposome following internalization into the endosomal compartment is one of the significant limitations to conventional liposomal drug delivery systems [1]. The encapsulated drug in the liposome must reach into the cell cytoplasm through two membranes, one of the liposomes itself and other of the endosome, while avoiding degradation in the lysosomal environment. A possible solution for achieving endosomal escape and intracellular drug delivery is provided by pH sensitive cell-penetrating peptides. We have utilized a single giant unilamellar vesicle assay to study the kinetics of pH sensitive cell-penetrating peptide induced pore formation in vesicles. Moreover, kinetics of peptide induced leakage at single vesicle level, mechanism of pore formation in phospholipid bilayer, estimation of the rate constant of pore formation, and rate of increase in pore density as a function of peptide concentration addressed in our studies will also be discussed.

Rapid clearance of liposomes from the circulatory system is another major limitation associated with liposomes. Chitosan, a cationic linear polysaccharide has been widely used in polymer based liposomal drug delivery system because of its biodegradability, biocompatibility, non-toxicity, and mucoadhesive properties. In this study, chitosan-bearing giant unilamellar vesicles were prepared using inverse phase precursor method. We measured mechanical properties such as bending and area compressibility moduli and lysis tension using micropipette aspiration assay [2]. Our findings demonstrate that incorporation of chitosan in phospholipid bilayers modulates the mechanical and transport properties of liposomes, which may affect their in vivo circulation time and drug release rate. Collectively, a deep understanding of the interaction of polymers and cell-penetrating peptides with phospholipid bilayer may help in designing an efficient liposomal drug delivery platform.

[1] T.M. Allen, P.R. Cullis, Liposomal drug delivery systems: From concept to clinical applications, Adv. Drug Deliv. Rev. 65 (2013) 36–48. doi:10.1016/j.addr.2012.09.037.

 

[2] H.P. James, S. Jadhav, Mechanical and transport properties of chitosan-zwitterionic phospholipid vesicles, Colloids Surfaces B Biointerfaces. 188 (2020) 110782.