Conjugation of materials to lipids can facilitate integration into the natural biological trafficking pathways for lipids – including association with lipoproteins and serum albumin. Integration into lipid trafficking pathways can enable controlled and targeted drug delivery. For example, therapeutic peptides such as insulin and GLP-1 agonists have been conjugated to lipids to promote albumin binding and prolong serum half-life. Lipidation of orally administered small molecule drugs can increase drug permeability, and facilitate association with intestinal lipoprotein trafficking pathways into lymph. Recently, lipid conjugation to adjuvants and antigens has been shown to enhance vaccine efficacy by increasing exposure to immune cells in lymph nodes by enabling ‘hitchhiking’ onto albumin trafficking pathway into lymph following injection. Our group has been working on a range of lipid conjugated materials, including orally administered lipid prodrugs of small molecule drugs and lipid conjugated oligonucleotides, peptides and brush PEG polymers administered via injection. Lipid conjugation alters the biodistribution and pharmacokinetics of these therapeutics in surprising ways, and in particular, promotes lymphatic uptake by facilitating integration into endogenous lipoprotein and albumin trafficking pathways into lymph. In this presentation I will highlight the relationships between the nature of the conjugated lipid and the pharmacokinetic outcomes, and the attendant benefits of lipid conjugated materials for vaccines and therapeutics to treat diseases involving the lymphatics, with a focus on immune and metabolic diseases.

Lipid conjugated materials to enhance drug delivery to lymph

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.