Design of Lipid and Polymeric Carriers for Nucleic Acid Delivery
type: CreativeWork
description: The objectives of the study were to investigate and develop lipid and polymeric carriers for nucleic acid delivery. These included: i) to develop novel cationic lipids for plasmid, oligonucleotide, and siRNA delivery; ii) to develop a novel polymeric delivery system, polyethylene glycol (PEG) based bio–conjugate, for oligonucleotide delivery; iii) to develop a novel bio–conjugate delivery system for siRNA delivery. In Chapter 2, we discussed the barriers and strategies of nucleic acid delivery, as well as summarized the commonly used lipids, polymers, and the corresponding carriers in terms of their characteristics, applications, advantages and limitations. Cationic lipids are most commonly used transfection reagents in delivery of nucleic acids to target cells in vitro. In Chapter 3, we synthesized a series of pyridinium lipids which contain a heterocyclic ring and a nitrogen atom. The structure–activity relationship (SAR) and formulation of corresponding cationic liposomes were studied for gene and siRNA delivery. The pyridinium lipids were mixed with a co–lipid, such as 1,2–dioleoyl–sn–glycero–3–phosphoethanolamine (DOPE) and cholesterol, to prepare cationic liposomes by sonication. These liposomes were mixed with plasmid DNA and transfected into CHO cells. Several factors including hydrophobic anchor chain length, anchor chain type, configuration of double bond, linker type, co–lipid type, cationic lipid/co–lipid molar ratio, charge ratio (N/P), concentration of serum, and cell type had significant influence on transfection efficiency and cytotoxicity. Pyridinium lipids with amide linker showed higher transfection efficiency compared to their ester counterparts. Liposomes prepared at a 1:1 molar ratio of pyridinium lipid and co–lipid showed higher transfection efficiency. Pyridinium lipids based on a hydrophobic anchor chain length of 16 showed higher transfection efficiency and lower cytotoxicity. The trans–isomers of pyridinium lipids showed higher transfectio…
abstract: The objectives of the study were to investigate and develop lipid and polymeric carriers for nucleic acid delivery. These included: i) to develop novel cationic lipids for plasmid, oligonucleotide, and siRNA delivery; ii) to develop a novel polymeric delivery system, polyethylene glycol (PEG) based bio–conjugate, for oligonucleotide delivery; iii) to develop a novel bio–conjugate delivery system for siRNA delivery. In Chapter 2, we discussed the barriers and strategies of nucleic acid delivery, as well as summarized the commonly used lipids, polymers, and the corresponding carriers in terms of their characteristics, applications, advantages and limitations. Cationic lipids are most commonly used transfection reagents in delivery of nucleic acids to target cells in vitro. In Chapter 3, we synthesized a series of pyridinium lipids which contain a heterocyclic ring and a nitrogen atom. The structure–activity relationship (SAR) and formulation of corresponding cationic liposomes were studied for gene and siRNA delivery. The pyridinium lipids were mixed with a co–lipid, such as 1,2–dioleoyl–sn–glycero–3–phosphoethanolamine (DOPE) and cholesterol, to prepare cationic liposomes by sonication. These liposomes were mixed with plasmid DNA and transfected into CHO cells. Several factors including hydrophobic anchor chain length, anchor chain type, configuration of double bond, linker type, co–lipid type, cationic lipid/co–lipid molar ratio, charge ratio (N/P), concentration of serum, and cell type had significant influence on transfection efficiency and cytotoxicity. Pyridinium lipids with amide linker showed higher transfection efficiency compared to their ester counterparts. Liposomes prepared at a 1:1 molar ratio of pyridinium lipid and co–lipid showed higher transfection efficiency. Pyridinium lipids based on a hydrophobic anchor chain length of 16 showed higher transfection efficiency and lower cytotoxicity. The trans–isomers of pyridinium lipids showed higher transfectio…
author: Zhu, Lin
keywords: delivery, lipid, nucleic acid, PEG, polymer, siRNA, Medicine and Health Sciences, Pharmaceutics and Drug Design, Pharmacy and Pharmaceutical Sciences
date published: 2010-12-01T08:00:00Z
date modified: 2026-07-24T05:00:23Z
provider: University of Tennessee Health Science Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Tennessee Health Science Center