Low density lipoproteins as drug carriers in the therapy of macrophage-associated diseases.
Low density lipoproteins (LDL) are internalised by the LDL receptor, which is expressed on the surface of eucaryotic cells. Metabolisation and chemical modification of LDLs lead to a shift in receptor affinity: modified LDLs are internalised through scavenger receptors, which are expressed on cells of the monocyte/ macrophage lineage. Coupling of substances with pharmacological activity, such as azidothymidine, to LDL results in a cell specific uptake of these drugs into macrophages by the scavenger receptor. Thus, drug-LDL derivatives might work as tools for macrophage specific drug targeting. In this context, it is essential to know the drug binding capacity, the optimal derivatization conditions, and the amount of drug molecules covalently bound to the LDL particle. In this study, we compared methods for optimal derivatisation and estimation of coupling efficiency, such as semi-quantitative lipoprotein gel electrophoresis, ultraviolet (UV) spectrophotometry, radiometric quantification, and specific protein hydrolysis.
Mankertz
J
J
Institut für Biochemie, Freie Universität Berlin, Germany. mankertz@zedat.fu-berlin.de
Nündel
M
M
von Baeyer
H
H
Riedel
E
E
D000596:Amino Acids / Q000032:analysis; D004337:Drug Carriers; D004587:Electrophoresis, Agar Gel; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000627:therapeutic use*; D008264:Macrophages / Q000378:metabolism*; D012588:Scintillation Counting; D013056:Spectrophotometry, Ultraviolet
D000596:Amino Acids; D004337:Drug Carriers; D008077:Lipoproteins, LDL