Theoretical model to describe formation and stability of liposome-drug complexes

Prof. Dr. S. May1), North Dakota State University/USA

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1.

Prof. Dr. Sylvio MayDepartment of Physics, North Dakota State University (NDSU), Fargo/USA

People involved

Rachel Downing (PhD fellow sponsored by the PRC)

Abstract

Despite the generally recognized relevance of applying theoretical concepts to the design of lipid-based drug carrier systems, there is little ongoing research to develop new and further refine existing concepts. We therefore propose to develop a variety of theoretical models for the interaction between drug molecules and liposomes.1)2) Four specific projects will be addressed: (i) the influence of membrane-intercalating drug molecules on the stability of liposomes, (ii) the conformation of vesicles containing polyethylene glycol (PEG)-lipids studied using theory and computer simulations, (iii) the impact of drug molecules on the dynamics of vesicle formation, and (iv) the kinetics of drug release from liposomes in spatially inhomogeneous systems.

We aim to extract and understand general physical mechanisms that relate to the formation and stability of drug-hosting liposomes.3)4)5) Hence, the result of this research will be the identification of mechanistic insights and the characterization of design principles for drug-containing liposomes. Our strategic goal is to re-emphasize the importance of theoretical research in the field of phospholipid vesicles and establish a culture of making models transparent and available to researchers.

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References:
1.
Douroumis D, Fahr A, 2012
Drug delivery strategies for poorly water-soluble drugs
John Wiley & Sons
2.
Allen TM, Cullis PR, 2013
Liposomal drug delivery systems: from concept to clinical applications
Adv. Drug Deliv. Rev. 65, 36-48
3.
Shai Y, 2002
Mode of action of membrane active antimicrobial peptides
Biopolymers 66, 236-248
4.
Seifert U, 1997
Configurations of fluid membranes and vesicles
Adv. Phys. 46, 13-137
5.
Lee MW, Han M, Bossa GV, Snell C, Song Z, Tang H, Yin L, Cheng J, May S, Luijten E, Wong GC, 2017
Interactions between Membranes and “Metaphilic” Polypeptide Architectures with Diverse Side-Chain Populations
ACS nano 11, 2858-2871
Publications derived from the project:
1.
Bossa GV, Gunderson S, Downing R, May S, 2019
Role of Transmembrane Proteins for Phase Separation and Domain Registration in Asymmetric Lipid Bilayers
Biomolecules 9, 303
2.
Rufeil Fiori E, Downing R, Bossa GV, May S, 2020
Influence of Spontaneous Curvature on the Line Tension of Phase-Coexisting Domains in a Lipid Monolayer: A Landau-Ginzburg Model
J. Chem. Phys. 152, 054707
3.
Downing R, Bossa GV, May S, 2020
Saddle-curvature instability of lipid bilayer induced by amphipathic peptides: A molecular model
Soft Matter 16, 5032-5043
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