Investigate the effects of molecular structure of lipidoids on self-assembly behavior.
library approach has been used to synthesize cationic lipid-based nanoparticles for
developing new drug delivery system. Even though it is useful to identify the synthetic
lipids with high efficiency, the fundamental mechanism of the structure-function
correlation of the cationic lipids remains to be illustrated. In this thesis, I
primarily investigated the structure o... read moref the self-assembled cationic lipids using a
combination of experimental and theoretic approaches, with an attempt to understand the
mechanism of the varied delivery efficacy between lipids with similar structures. I used
the fluorescence spectrometer measured the Critical Micelle Concentration (CMC) of the
lipids from the library. The effects of the head group, disulfide bond and the length of
the alkyl chains on the self-assembly behavior of the synthetic lipids were thoroughly
investigated. Meanwhile, atomic force microscope (AFM) is used to study the morphology
of the self-assembled lipid system. I also attempted to study the self-assembly of the
lipids using molecular dynamic (MD) simulation. MD simulations showed that the synthetic
lipids could aggregate in solution. The stability of the bilayer structure in simulation
also indicated that the micelles or liposomes formed by lipidoids can maintain stability
in aqueous solution. The future work will contain several sections, including: i) to
correlate the experimental study and MD simulation to illustrate the different
self-assembly of various lipids with similar structures; ii) to generate an approach for
rationale design the lipids with efficient delivery
Thesis (M.S.)--Tufts University, 2015.
Submitted to the Dept. of Biomedical Engineering.
Advisor: Qiaobing Xu.
Committee: Tim Atherton, and Mark Cronin-Golomb.
Keyword: Biomedical engineering.read less