Designer lipids for drug delivery: From heads to tails

JOURNAL OF CONTROLLED RELEASE

卷:190

Review

Kohli, Aditya G.^1,2  Kierstead, Paul H.³  Venditto, Vincent J.²  Walsh, Colin L.^1,2  Szoka, Francis C.^1,2 

[1] Univ Calif Berkeley, UC Berkeley UCSF Grad Program Bioengn, Berkeley, CA 94720 USA

[2] Univ Calif San Francisco, Dept Bioengn Therapeut Sci & Pharmaceut Chem, San Francisco, CA 94143 USA

[3] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

关键词: Biophysics;    Immunology;    Liposomes;    Payload release;    Targeting;   

DOI  :  10.1016/j.jconrel.2014.04.047

来源: Elsevier

【 摘 要 】

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. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free