Synthetic Lipids for Drug Delivery Applications

Date

2015-09-23

Authors

Meanwell, Michael Weiwei

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Abstract

Solid lipid nanoparticles (SLNPs) and lipid-drug conjugates (LDCs) are two promising lipid nanoparticle (LNP) based drug delivery systems; this thesis explores new synthetic lipids that may circumvent the limitations of currently available components for LNPs with particular focus on the stability of LNP formulations. Neutral polyethylene glycol lipids (PEG-lipids) have been designed, synthesized, and characterized with ESI-MS, for stabilizing SLNPs containing dsDNA oligomer. 1st and 2nd generation PEG-lipids investigated the effects of serinol and iminodiacetic acid backbone structures, respectively, and aliphatic chain sequences within the lipid anchors on the stability of SLNPs. Assays were developed to analyze LNP stability in both PBS buffer and PBS buffer with 10 % serum at different incubation temperatures. The results indicate that the hydrocarbon branching sequence offer additional SLNP stability over straight chain isomers. LDC monomers were designed and synthesized to allow for the formulation of LDC nanocarriers for the thiopurine drugs. These hydrophobic LDC monomers were made by linking the polar thiopurine drug to a synthetic lipid. These synthetic lipids investigated branched and straight chain derivatives – the branched isomers once again demonstrated advantages in the stability of the LDCs.

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Keywords

Drug delivery, Organic chemistry, Medicinal chemistry, Synthetic lipids, Lipid nanoparticles, Particle stability

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