Rational design of liposomal drug delivery systems, a review: Combined experimental and computational studies of lipid membranes, liposomes and their PEGylation
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
26915693
DOI
10.1016/j.bbamem.2016.02.025
PII: S0005-2736(16)30055-4
Knihovny.cz E-resources
- Keywords
- Drug delivery, Label-free analytics, Liposome, Molecular dynamics simulation, Nanomedicine, PEGylation,
- MeSH
- Drug Delivery Systems * MeSH
- Lipid Bilayers chemistry MeSH
- Liposomes * MeSH
- Membrane Lipids chemistry MeSH
- Quartz Crystal Microbalance Techniques MeSH
- Polyethylene Glycols MeSH
- Scattering, Radiation MeSH
- Molecular Dynamics Simulation * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Lipid Bilayers MeSH
- Liposomes * MeSH
- Membrane Lipids MeSH
- Polyethylene Glycols MeSH
Combined experimental and computational studies of lipid membranes and liposomes, with the aim to attain mechanistic understanding, result in a synergy that makes possible the rational design of liposomal drug delivery system (LDS) based therapies. The LDS is the leading form of nanoscale drug delivery platform, an avenue in drug research, known as "nanomedicine", that holds the promise to transcend the current paradigm of drug development that has led to diminishing returns. Unfortunately this field of research has, so far, been far more successful in generating publications than new drug therapies. This partly results from the trial and error based methodologies used. We discuss experimental techniques capable of obtaining mechanistic insight into LDS structure and behavior. Insight obtained purely experimentally is, however, limited; computational modeling using molecular dynamics simulation can provide insight not otherwise available. We review computational research, that makes use of the multiscale modeling paradigm, simulating the phospholipid membrane with all atom resolution and the entire liposome with coarse grained models. We discuss in greater detail the computational modeling of liposome PEGylation. Overall, we wish to convey the power that lies in the combined use of experimental and computational methodologies; we hope to provide a roadmap for the rational design of LDS based therapies. Computational modeling is able to provide mechanistic insight that explains the context of experimental results and can also take the lead and inspire new directions for experimental research into LDS development. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
References provided by Crossref.org
Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery
Tail-Oxidized Cholesterol Enhances Membrane Permeability for Small Solutes
