title: Designer lipids for drug delivery: from heads to tails.
abstract: For four decades, liposomes composed of both naturally occurring and synthetic lipids have been investigated as delivery vehicles for low molecular weight and macromolecular drugs. These studies paved the way for the clinical and commercial success of a number of liposomal drugs, each of which required a tailored formulation; one liposome size does not fit all drugs! Instead, the physicochemical properties of the liposome must be matched to the pharmacology of the drug. An extensive biophysical literature demonstrates that varying lipid composition can influence the size, membrane stability, in vivo interactions, and drug release properties of a liposome. In this review we focus on recently described synthetic lipid headgroups, linkers and hydrophobic domains that can provide control over the intermolecular forces, phase preference, and macroscopic behavior of liposomes. These synthetic lipids further our understanding of lipid biophysics, promote targeted drug delivery and improve liposome stability. We further highlight the immune reactivity of novel synthetic headgroups as a key design consideration. For instance it was originally thought that synthetic PEGylated lipids were immunologically inert; however, it's been observed that under certain conditions PEGylated lipids induce humoral immunity. Such immune activation may be a limitation to the use of other engineered lipid headgroups for drug delivery. In addition to the potential immunogenicity of engineered lipids, future investigations on liposome drugs in vivo should pay particular attention to the location and dynamics of payload release.
authors.affiliation: The UC-Berkeley-UCSF Graduate Program in Bioengineering, University of California Berkeley, Berkeley 94720, USA; Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA.
authors.forename: Aditya G
authors.initials: AG
authors.lastname: Kohli
authors.affiliation: Department of Chemistry, University of California, Berkeley 94720, USA.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Kierstead
authors.affiliation: Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Venditto
authors.affiliation: The UC-Berkeley-UCSF Graduate Program in Bioengineering, University of California Berkeley, Berkeley 94720, USA; Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Walsh
authors.affiliation: The UC-Berkeley-UCSF Graduate Program in Bioengineering, University of California Berkeley, Berkeley 94720, USA; Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco 94143, USA. Electronic address: szoka@cgl.ucsf.edu.
authors.forename: Francis C
authors.initials: FC
authors.lastname: Szoka
mesh_terms: D003692:Delayed-Action Preparations; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D011108:Polymers
chemical_list: D003692:Delayed-Action Preparations; D008055:Lipids; D008081:Liposomes; D011108:Polymers
keywords: Biophysics; Immunology; Liposomes; Payload release; Targeting