Recombinant lipoproteins: lipoprotein-like lipid particles for drug targeting

被引:183
作者
Rensen, PCN
de Vrueh, RLA
Kuiper, J
Bijsterbosch, MK
Biessen, EAL
van Berkel, TJC
机构
[1] Leiden Univ, Amsterdam Ctr Drug Res, Sylvius Labs, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
[2] OctoPlus BV, NL-2333 CL Leiden, Netherlands
关键词
antisense oligo(deoxy)nucleotide; apolipoprotein; chylomicron; emulsion; gene delivery; HDL; hepatocyte; LDL; lipopolysaccharide; liposome; nucleoside analog; prodrug; therapy;
D O I
10.1016/S0169-409X(01)00109-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Lipoproteins are endogenous particles that transport lipids through the blood to various cell types, where they are recognised and taken up via specific receptors. These particles are, therefore, excellent candidates for the targeted delivery of drugs to various tissues. For example, the remnant receptor and the asialoglycoprotein receptor (ASGPr), which are uniquely localised on hepatocytes, recognise chylomicrons and lactosylated high density lipopoteins (HDL), respectively. In addition, tumour cells of various origins overexpress the low density lipoprotein (LDL) receptor that recognises apolipoprotein E (apoE) on small triglyceride-rich particles and apoB-100 on LDL. Being endogenous, lipoproteins are biodegradable, do not trigger immune 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 successfully synthesised recombinant lipoproteins from commercially available natural and synthetic lipids and serum-derived or recombinant apolipoproteins, which closely mimic the metabolic behaviour of their native counterparts in animal models as well as humans. In this paper, we will summarise the studies that led to the development of these recombinant lipoproteins, and we will 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 activities of recombinant chylomicrons and HDL in sepsis and atherosclerosis will be discussed. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:251 / 276
页数:26
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