Recombinant lipoproteins: lipoprotein-like lipid particles for drug targeting

Lipoproteins are endogenous particles that transport lipids through the blo od to various cell types, where they are recognised and taken up via specif ic receptors. These particles are, therefore, excellent candidates for the targeted delivery of drugs to various tissues. For example, the remnant rec eptor and the asialoglycoprotein receptor (ASGPr), which are uniquely local ised on hepatocytes, recognise chylomicrons and lactosylated high density l ipopoteins (HDL), respectively. In addition, tumour cells of various origin s overexpress the low density lipoprotein (LDL) receptor that recognises ap olipoprotein E (apoE) on small triglyceride-rich particles and apoB-100 on LDL. Being endogenous, lipoproteins are biodegradable, do not trigger immun e reactions, and are not recognised by the reticuloendothelial system (RES) . However, their endogenous nature also hampers large-scale pharmaceutical application. In the past two decades, various research groups have successf ully synthesised recombinant lipoproteins from commercially available natur al and synthetic lipids and serum-derived or recombinant apolipoproteins, w hich closely mimic the metabolic behaviour of their native counterparts in animal models as well as humans. In this paper, we will summarise the studi es that led to the development of these recombinant lipoproteins, and we wi ll address the possibility of using these lipidic particles to selectively deliver a wide range of lipophilic, amphiphilic, and polyanionic compounds to hepatocytes and tumour cells. In addition, the intrinsic therapeutic act ivities of recombinant chylomicrons and HDL in sepsis and atherosclerosis w ill be discussed. (C) 2001 Elsevier Science B.V. All rights reserved.