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theses

As important drug delivery vehicles, liposomes have received extensive attention when being used to encapsulate both hydrophobic and hydrophilic drugs. In order to increase their colloidal stability, poly(ethylene glycol) (PEG) modified amphiphilic molecules(AM) are inserted in the lipid bilayer to form a PEG shell to protect liposomes from aggregation. However, the influence of amphiphile hydrophobic tail unsaturation and hydrophobe conformation are not well studied. Hence in this project, lipid bilayers grafted with a series of AM in different concentrations(2%, 4% and 6%) are built and simulated by using DRY MARTINI Coarse-Grained(CG) Force Field(FF) to capture the impact of amphiphile hydrophobic tail unsaturation and hydrophobe conformation. Our computational research is performed in collaboration with experimental research which synthesized DSPC liposomes with AM to capture the liposome aggregation behavior and membrane permeability. Our finding shows that with the increasing of AM tail unsaturation, there will be more disorders in AM hydrophobic tails. Those disorders decrease the colloidal stability of liposomes. Also with increasing AM concentration in the system, the corona of PEG will be thicker and the distribution of PEG beads becomes more uniform. Those give the iii liposome a better protection against each other due to the steric repulsion of PEG. This protection increases the colloidal stability of liposomes and finally make the aggregation of liposomes slower. The outcome of this study combined with experimental results can guide the design of drug delivery liposomes. In addition, the analysis routines developed during the course of this study will contribute to suite of computational tools which is being developed for future studies.

ETD_8264

M.S.

Includes bibliographical references

by Bin Zhang

doi:10.7282/T3RV0RVV

ETD graduate

The author owns the copyright to this work.