Combinatorial Study of Lipid-like Materials for Gene Delivery.
evaluation of a library of lipidoids for in vitro DNA delivery through a facile
combinatorial approach was investigated. The mild reactions between amines and
acrylamides, acrylates, or epoxides enabled the construction of a library to screen for
efficient gene delivery carriers. In Chapter 2, a combinatorial library of lipidoids was
constructed and studied for in vitro gene del... read moreivery. The library of lipidoids was
synthesized by reacting commercially available amines with lipophilic acrylates,
acrylamides, or epoxides. Lipidoids derived from amine 86
(N,N-Bis(2-hydroxyethyl)ethylene diamine) and amine 87 (N-(3-aminopropyl)diethaneamine)
showed high efficiency in DNA delivery, some with a higher transfection efficiency than
Lipofectamine 2000, a commonly used commercial gold standard for in vitro gene delivery.
The structure-activity relationship between the lipidoids was further studied with
respect to small variations in chemical structures and the resulting efficiency in DNA
delivery in vitro. Since these lipidoids are easy to synthesize and do not require a
co-lipid for efficient DNA delivery, they could offer an inexpensive but effective
alternative to other commonly used commercial gene delivery carriers. This Chapter 3
describes the synthesis of a combinatorial library of quaternized lipidoids and the
evaluation of their abilities to facilitate in vitro DNA delivery. By formulating
liposomes with a neutral helper lipid, 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine
(DOPE), the quaternized lipidoids can significantly enhance their gene transfection
abilities due to the weaken quaternized lipidoid and DNA binding and the hexagonal-phase
forming propensity of liposomes. We further optimized the liposome composition and DNA
dose for gene transfection and investigated the structure-activity relationships of the
lipidoid library in DNA delivery.
Thesis (M.S.)--Tufts University, 2012.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: Qiaobing Xu.
Committee: Qiaobing Xu, David Kaplan, and Kyongbum Lee.
Keyword: Chemical engineering.read less